Showing papers on "Antigen published in 1975"

Rapid isolation of antigens from cells with a staphylococcal protein A-antibody adsorbent: parameters of the interaction of antibody-antigen complexes with protein A.

Abstract: The Cowan I strain of the bacterium Staphylococcus aureus has been used as an adsorbent for antibodies complexed with radiolabeled antigens from cell lysates. This application is advanced as a superior alternative to other methods of immune precipitation for the isolation of antigens. It exploits the high adsorption capacity for IgG molecules by protein A molecules on the cell walls of certain strains of staphylococci, along with the advantageous sedimentation properties of the bacteria. The interaction of immune complexes with the adsorbent was defined initially using a model system of bovine serum albumin with a high excess of rabbit anti-bovine serum albumin antibodies (IgG). The uptake of immune complexes under these conditions was extremely rapid, occurring within seconds, whereas maximum binding of free IgG was much slower. In addition, once bound the complexed antigen could not be displaced from the adsorbent either by large amounts of normal IgG or by extra free antibody. Antigen could be eluted almost completely from the inert adsorbent for analytic or preparative purposes with a variety of solvent systems, such as the detergent SDS in combination with urea and high temperature, and neutral salts with strong lyotropic salting in properties. The efficacy of the protein A-antibody adsorption technique was tested in direct comparisons with a conventional double antibody precipitation method for the isolation of mouse lymphocyte IgM. The bacterial adsorbent not only had a distinct advantage in speed of antigen isolation, but analyses by polyacrylamide gel electrophoresis in SDS also revealed consistently higher antigen recoveries, lower levels of background radioactivity, and an absence of other cell components which may nonspecifically bind to and complicate analyses using conventional immune precipitates.

Natural cytotoxic reactivity of mouse lymphoid cells against syngeneic and allogeneic tumors. I. Distribution of reactivity and specificity

Abstract: Lymphoid cells from many normal mice of a variety of inbred strains were found to have reactivity, in a 51Cr release cytotoxicity assay, against several syngeneic and allogeneic tumors. Very high reactivity was seen with effector cells from athymic nude mice, which was consistent with other evidence that the reactivity was not T-cell dependent. Target cells susceptible to lysis included tumors induced by oncogenic type-C viruses but also tumors induced by other means and expressing endogenous type-C viruses. The levels of natural reactivity were influenced by age, with highest cytotoxicity produced by cells from 5- to 8-week-old mice. Lymph-node cells, spleen cells, peritoneal exudate cells and peripheral blood lymphocytes all had cytotoxic reactivity. The specificity of the reactions was analyzed in detail by ana inhibition assay. Evidence was obtained for natural reactivty against several different antigens, each apparently associated with expression of murine endogenous type-C viruses.

Functional subclasses of T-lymphocytes bearing different Ly antigens. I. The generation of functionally distinct T-cell subclasses is a differentiative process independent of antigen.

Abstract: Ly alloantigens coded by two unlinked genetic loci (Ly-1 and Ly-2/Ly-3) are expressed on lymphoid cells undergoing thymus-dependent differentiation. Peripheral Thy-1+ cells from C57BL/6 mice can be divided into three subclasses on the basis of differential expression of Ly-1, Ly-2, and Ly-3; about 50% express all three Ly antigens (Ly -123+), about 33% only Ly-1 (Ly-1+), and about 6-8% Ly-2 and Ly-3 (Ly-23+). Cells of the Ly-123+ subclasses are the first peripheral Thy-1+ cells to appear in ontogeny, and are reduced in the periphery shortly after adult thymectomy. In contrast, Ly-1+ and Ly-23+ subclasses appear later in the peripheral tissues than do Ly-123+ cells, and are resistant to the early effects of adult thymectomymperiheral lymphoid populations depleted of Ly-1+ cells and Ly-123+ cells (and thereby enriched for Ly-23+ cells) were incapable of developing significant helper activity to SRBC but generated substantial levels of cytotoxic activity to allogeneic target cells. The same lymphoid populations, depleted of Ly-23+ cells and Ly-123+ cells (and thereby enriched for Ly-1+ cells), produced substantial helper responses but were unable to generate appreciable levels of killer activity. These experiments imply that commitment of T cells to participate exclusively in either helper or cytotoxic function is a differentiative process that takes place before they encounter antigen, and is accompanied by exclusion of different Ly groups, Lu-23 or Ly-1 respectively, from TL+Ly-123+ T-cell precursors. It is yet to be decided whether the TL-phase by Ly-123+ subclass is a transitional form or a separately differentiated subclass with a discrete immunologic function.

Vertical transmission of hepatitis B antigen in Taiwan.

Abstract: To determine the frequency of vertical transmission of hepatitis B antigen (HB5 Ag) from asymptomatic carrier mothers in Taiwan to their offspring, HB5 Ag was sought by radioimmunoassay and complement fixation. Of 158 babies born to carrier mothers, antigenemia developed in 63; 51 of these antigenemic babies had become antigen positive within the six months of life. Three inter-related factors were found to increase the risk that antigenemia would develop in the infant: a high maternal complement-fixation titer for HB5 Ag: presence of HB5 Ag in the baby's umbilical-cord blood: and antigenemia in siblings. In contrast to previous studies, these findings indicate that vertical transmission from carrier mothers frequently occurs, at least in Taiwan, and may partially explain Taiwan's high prevalence of HB5 Ag.

The H-2 major histocompatibility complex and the I immune response region: genetic variation, function, and organization.

Abstract: Publisher Summary One of the most rapidly developing areas of immunologic research deals with the H-2 gene complex, a tightly linked series of genes controlling a variety of immunologic traits, including histocompatibility and immune responsiveness. This chapter summarizes the varieties of phenotypic traits associated with differences in the H-2 complex. The mapping of the H-2 complex into four major regions marked by H-2K, Ir-1, Ss-Slp, and H-2D genes plus the associated Tla gene is discussed in the chapter, along with the phenotypic traits associated with these regions. The chapter discusses the immune response region, the genes of which appear to control a variety of immune phenomena—including antibody response to many antigens, susceptibility to tumor viruses, and graft-versus-host (GVH), and mixed lymphocyte culture (MLC) reactions. The H-2 complex consists of many genes with diverse functions, most of which control cell membrane structures and/or processes. The fact that lymphocytes are particularly affected by H-2 genes has important implications for immunology. However, some of the genes also affect other cell types, implying a still larger role for the H-2 complex, perhaps in development or in cell regulation. Because the H-2 complex is the most thoroughly characterized segment of a mammalian chromosome, it is also an important model for the studies of gene action, organization, and evolution in mammals.

Electrophoretic method of detecting antigen-antibody reaction

Abstract: A method of rapidly detecting presence of antibodies in a solution comprises depositing, on each of a plurality of microscopic particles, an antigen specific to the antibodies sought, and forming a dilute suspension of the particles in the solution to be examined. The suspension is stirred, and electrophoretic mobility of the particles is measured upon formation of the suspension and measured again at a subsequent time. Detection of a change in electrophoretic mobility of the particles between the two measurements indicates presence of the antibodies in the solution.

Enhanced immunological surveillance in mice heterozygous at the H-2 gene complex.

Abstract: THE major histocompatibility (H) antigens of higher animals show extreme genetic polymorphism equalled, in higher vertebrates, only by that associated with the immunoglobulins1. Maintenance of such a high rate of variability implies evolutionary advantage for heterozygotes in the HL-A system for man, or at the H-2 gene complex in mice2,3. We propose a possible selective mechanism, based on the realisation that immunological surveillance function (defined here as recognition and elimination of modified host cells by sensitised thymus-derived lymphocytes (T-cells) may be considerably enhanced in mice heterozygous at the H-2 gene complex.

H-2 compatability requirement for T-cell-mediated lysis of target cells infected with lymphocytic choriomeningitis virus. Different cytotoxic T-cell specificities are associated with structures coded for in H-2K or H-2D;.

Abstract: Use of syngeneic, allogeneic, F1, AND H-2 recombinatn mice has shown that animals injected with lymphocytic choriomeningitis (LCM) virus generate T cells which are cytotoxic for H-2K or H-2D compatible, but not H-2 different, virus-infected target cells. Three separate lines of evidence are presented which indicate that these immune T cells are sensitized to "altered-self," the self antigens involved being coded for in the H-2K or H-2d regions. Firstly, cytotoxic activity associated with mutuality at H-2D iy, lysis mediated by immune T cells from F1 or H-2 recombinant mice is specifically inhibited only by presence of unlabeled, virus-infected cells that are H-2 compatible with the targets. Thirdly, LCM-immune F1 and H-2 recombinant T cells inoculated into irradiated, virus-infected recipients proliferate only to kill target cells that are H-2 compatible with both the donor and the recipient. All of these experiments establish that there is a dissociation of T-cell activities between parental haplotypes in F1 mice, and between H-2K and H-2D in recombinants. It would thus seem that there are at least two specificities of tlcm-immune T cells in homozygotes, associated with either H-2K or H-2D, and four specificities in F1 hybrids. The significance of these findings, with respect both to gene duplication and to the marked polymorphism in the H-2 system, is discussed.

A new analysis of allogeneic interactions.

Abstract: Allogeneic reactions have conventionally been considered as typical immune responses by one population of cells to antigens present on the other. This view is inadequate, since it does not explain many features of these reactions, among which are: (1) reactivity is much higher between different strains within a species than between species, in spite of the much greater antigenic disparity in the second case; (2) a very high proportion of cells may respond to allogeneic stimuli; (3) major histocompatibility differences are not essential for vigorous allogeneic reactions; (4) the responding population need not be immunologically competent to respond to antigens of the stimulating population; (5) the stimulating population must be both metabolically active and immunocompetent. We have tried to produce a model of cell interaction which will account for these and other anomalies, which at the same time explaining both normal antigenic stimulation (through cell-cell cooperation) and allogeneic interactions as examples of the same basic mechanisms. The model is based on the Bretscher-Cohn scheme of cell interaction. An allogeneic reaction is seen as having two stages: (1) Cells come together when antibody receptors on cells of one population combine with antigens on cells of the other. To this extent, our model is the same as the conventional one. It need not be the responding population which has the receptors, however. (2) A species-specific proliferation signal passes between the cells. This is the same signal as is involved in normal antibody induction. Even antigen-receptor bonds which are very weak may result in effective stimulation of one or both partners because of enhancing effect of this signal, and because the antigens involved are probably repeated over the cell surface, enabling multipoint binding. This explains the very proportions of cells which proliferate. The exact outcome of any allogeneic interaction will depend on which of the two populations have antibody receptors for antigens on the other, which can produce the proliferative stimulus, and which can respond to either the proliferative signal alone or to this stimulus plus antigen.

Transfusion-associated hepatitis not due to viral hepatitis type A or B.

Abstract: Twenty-two patients who had an episode of transfusion-associated hepatitis not positive for hepatitis B antigen were examined for development of antibody to heaptitis A and B antigens, cytomegalovirus and Epstein-Barr virus. Antibody response to the 27-nm virus-like hepatitis A antigen was measured by immune electron microscopy. In none of the 22 patients studied did serologic evidence of infection with hepatitis A virus develop during the study period. Nine of the 22 patients had antibody responses to cytomegalovirus, but it was difficult to relate these seroconversions to their hepatitis. In addition, all 22 patients had pre-existing antibody to the Epstein-Barr virus. It seems likely that at least a proportion of such antigen-negative transfusion-associated hepatitis is caused by other infectious agents, not yet identified.

The major histocompatibility complex determines susceptibility to cytotoxic T cells directed against minor histocompatibility antigens.

Abstract: Cytotoxic cells were generated by immunizing one strain of mouse with cells from an allogeneic strain which carries the same H-2 region. The effector cells assayed in a 4 h 51Cr release assay were shown to be T cells and indistinguishable, except in specificity, from cytotoxic T cells directed at H-2 alloantigens. Although the genetic differences between responder and stimulator cells responsible for the immunization did not code in H-2, the H-2 complex did restrict susceptibility of target cells. For example, BALB.B cytotoxic cells (H-2b) immunized against and capable of lysing C57BL/6 cells (H-2b) would not lyse B6.C/H-2d target cells. C57BL/6 and B6.C/H-2d are congenic and differ in the H-2 region. Two hypotheses are considered to explain the H-2 restriction of susceptibility to cytotoxic T cells generated by an H-2 identical alloimmunization. (a) The dual (self) recognition hypothesis states that the cytotoxic cell has two recognition units, one for H-2-coded structures and another clonally restricted receptor for the minor alloantigen. (b) The interaction antigen hypothesis states that all the surface alloantigenic determinants recognized by cytotoxic T cells are the result of interaction between H-2- and non-H-2-coded gene products. Two lines of evidence, one with F1 effector cells and the other a cold target competition experiment, are presented which argue strongly in favor of the interaction antigen hypothesis. The regions of H-2 required to be histocompatible were mapped to the D region and to the left of IC, probably the K region. These results, and recent work on the response to virus-infected and TNP-modified syngeneic cells, suggest that cytotoxic cells are restricted in specificity to preferentially recognizing alterations in structures that are coded in the major histocompatibility complex.

In vitro cell-mediated immune responses to the male specific(H-Y) antigen in mice.

Abstract: C57BL/10 female mice were primed to the male specific antigen H-Y, either by grafting with syngeneic male tail skin or by ip injection of syngeneic male spleen cells Primed female spleen cells, either unseparated or filtered through nylon wool to remove most of the B lymphocytes, were then cultured for 5 days in vitro with irradiated syngeneic male spleen cells and assayed against 51Cr-labeled target cells Both unseparated and nylon wool filtered female cells displayed significant cytotoxic activity restricted to male target cells Pretreatment of sensitized female cells with antitheta serum and complement just before assay abolished cytotoxic responses We were unable to demonstrate cell-mediated cytotoxic responses into two nonresponding strains, CBA and B10A, which fail to reject male isografts The cytotoxic activity of C57BL/10 female cells was restricted to male target cells histocompatible with C57BL/10 over at least a portion of the major (H-2) histocompatibility complex We conclude that secondary in vitro cytotoxic responses against the H-Y antigen are mediated by cytotoxic T lymphocytes, and that the H-Y target cell antigen may be specified by the H-2 complex

Antibodies to cellular antigens in Sjögren's syndrome.

Abstract: An extract of human lymphocytes from continous cell culture was used as the antigen source to detect antibodies in sera of patients with Sjogren's syndrome (SS). Using double diffusion in agarose, 85 per cent of a selected group of patients had precepating antibodies. Three precipitating antigen-antibody systems were detected and were shown to be different from those described previously in othe systemic rheumatic diseases. The SS precipitating antibodies were temporarily classified as precipitins, A, B, and C. SS patinets with sicca syndrome but without clinical rheumatoid arthritis had precipitin systems A and/or B, and SS patients with associated rheumatoid arthritis had precipitin system C. Serum reactants were demonstrated by immuno-electrophoresis to migrate in the gamma globulin region. The precipitating activity of the serum factors was not destroyed by treatment with 2-mercaptoethanol and was not removed by absorption of rheumatoid factor from the sera. The reactivity of the lympuocyte antigens was destroyed by treatment with trypsin but not by deoxyribonuclease or ribonuclease.

Augmentation of delayed-type hypersensitivity by doses of cyclophosphamide which do not affect antibody responses.

Abstract: Mice immunized with more SRBC than are required to produce optimal delayed-type hypersensitivity reactions, developed good antibody responses and poor delayed foot pad reactions. Cyclophosphamide treatment in low doses (20 mg/kg) before immunization, augmented the delayed-type hypersensitivity without affecting antibody responses. Cyclophosphamide did not augment delayed responses to optimal doses of SRBC (0.01%), but did augment the delayed hypersensitivity response of mice immunized with a suboptimal antigen dose (0.001%); which produced no detectable antibody response with or without cyclophosphamide pretreatment. These results suggest that antibody feedback is not the sole regulator of delayed reactions; the possibility that suppressor T cells may also be involved is discussed.

Establishment and characterization of an Epstein-Barr virus (EBC)-negative lymphoblastoid B cell line (BJA-B) from an exceptional, EBV-genome-negative African Burkitt's lymphoma

Abstract: An Epstein-Barr virus (EBV)-negative lymphoblastoid cell line (LCL), BJA-B, was established from an African Burkitt's lymphoma (BL) which contained no detectable EBV DNA and did not express the EBV specified antigen EBNA, BJA-B cells grow in typically large, flat clumps. All carry surface-bound immunoglobulins, a B lymphocyte marker, and do not form rosettes with sheep erythrocytes. After infection of BJA-B cells by EBV the infected cells may produce either EBV-determined nuclear antigen (EBNA) or both EBNA and early antigen (EA), depending on the strain of EBV. The homogeneity of the BJA-B cell population with respect to immunological and isoenzyme markers and size suggests a clonal origin of the line. BJA-B is the first EBV-negative LCL established from an African Burkitt's lymphoma and demonstrates that an EBV-independent continuous B cell line can be established "in vitro" from other than leukemia or myeloma cells.

Cell-mediated lympholysis of trinitrophenyl-modified autologous lymphocytes. Effector cell specificity to modified cell surface components controlled by H-2K and H-2D serological regions of the murine major histocompatibility complex.

Abstract: Splenic lymphocytes from four C57BL/10 congenic resistant mouse strains were sensitized in vitro with trinitrophenyl (TNP)-modified autologous spleen cellsmthe effector cells generated were incubated with 51-Cr-labeled unmodified or TNP-modified spleen or tumor target cells, and the percentage of specific lympholysis determined The results obtained using syngeneic-, congenic-, recombinante, and allogeneic-modified target cells indicated that TNP modification of the target cells was a necessary but insufficient requirement for lympholysis Intra-H-2 homology either between modified stimulating cells and modified target cells or between responding lymphocytes and modified target cells was also important in the specificity for lysis Homology at the K serological region or at K plus I-A in the B10A and B10BR strains, and at either the D serological region or at some other region (possibly K) in the B10D2 and C57BL/10 strains were shown to be necessary in order to detect lympholysis Experiments using (B10itimes C57BL/10)F1 responding lymphocytes sensitized and assayed with TNP-modified parental cells indicated that the homology required for lympholysis was between modified stimulating and modified target cellsmthe possibility is raised that histocompatibility antigens may serve in the autologous system as cell surface components which are modified by viruses or autoimmune complexes to form cell-bound modified-self antigens, which are particularly suited for cell-mediated immune reactions Evidence is presented suggesting that H-2-linked Ir genes are expressed in the TNP-modified autologous cytotoxic system These findings imply that the major histocompatibility complex can be functionally involved both in the response potential to and in the formation of new antigenic determinants involving modified-self components

Multiple mouse-protective antibodies directed against group B streptococci. Special reference to antibodies effective against protein antigens.

Abstract: The data presented in this paper establish the finding that multiple specific protective antibodies exist in rabbits in response to immunization with Group B streptococci. The summary in Table I indicates the serological types into which Group B streptococci have been divided on the basis of their antigenic composition. This classification is dependent upon passive protection of mice with antibodies directed against the specific antigens, and types are defined in these terms. Heretofore, it was thought that type-specific polysaccharides accounted for all such protection in Group B streptococci. Certain exceptions of cross-protection between types due to minor polysaccharide determinants soon appeared; cross-protection reactions based on protein determinants in at least two types were also discovered. The present experiments show that specific antibodies directed to either polysaccharide or protein antigens of a single strain can be protective against infection with streptococci containing these antigens.

The role of macrophages in the generation of T-helper cells. II. The genetic control of the macrophage-T-cell interaction for helper cell induction with soluble antigens.

Abstract: Helper cell induction to nonparticle antigens in vitro requires the cooperation of T cells and macrophages, but does not occur if the macrophages are allogenic. The reasons for this were investigated. Malfunction of allogenic macrophages was excluded by cultures with their syngenic T cells; suppressor cell induction was excluded by admixture experiments. Thus, T cells and macrophages only cooperated if they were genetically similar. The genetic locus (loci) involved was mapped. Using congenic lines differing only at the H-2 complex, the genetic control of T-macrophage interaction was localized in the H-2 region. Mice with intra H-2 recombinants were used to map the T-macrophage interaction locus in the I-A region of the H-2 complex (formerly known as poly-D, L-ala-poly-L-lys. Recombinants were also used to exclude the presence of another T-macrophage locus either the K, I-B, or I-C, SS-Slp, or D regions of the H-2 complex. Genetic restrictions for T-macrophage interaction in helper cell induction was shown in mice of the H-2-k, d, b, q, s genotypes as well as in H-2 recombinants. The possible mechanisms and significance of this genetic restriction are discussed.

Suppression of the immune response by alpha-fetoprotein on the primary and secondary antibody response.

Abstract: Mouse amniotic fluid was shown to contain a noncytotoxic inhibitor of primary gammaM and secondary gammaM, gammaG subclass splenic plaque forming cells in vitro to SRBC. The suppressive effect was not abolished by exhaustive dialysis or by absorption of mouse amniotic fluid (MAF) with SRBC. Polyacrylamide gel analysis showed that dialyzed MAF was composed of three major protein components, transferrin, albumin, and alpha-fetoprotein (AFP). The selective removal of each of these patients from MAF by affinity chromatography suggested that AFP was the immunosuppressive substance in MAF. This conclusion was verified by the demonstration that pure AFP suppressed in vitro antibody synthesis in microgram quantities whereas equivalent amounts of normal mouse serum, transferrin, or albumin did not. Dose-response studies showed that the effect of AFP in the isolated form was equivalent to the suppressive effect of comparable amounts of AFP in MAF. gammaA and gammaG plaque-forming cell (PFC) responses were suppressed by a significantly lower concentration of AFP than was the gammaM PFC response. The degree of suppression watration of AFP than was the gammaM PFC response. The degree of suppression was dependent on the time at which AFP was added to the cultures; MAF added to antigen-stimulated cultures up to 24 h after initiation of cultures was immunosuppressive whereas similar additions of MAF at 48 h after initiation or later did not suppress. The duration of exposure of spleen cells to MAF in cultures without antigen necessary to achieve suppression of a subsequent primary immune response was determine-d to be approximately 8 h. The results suggest that AFP may have an immunoregulatry function. This has potentially important implications in the maternal-fetal relationship, the immune capabilities of the fetus and newborn, and in certain malignant and nonmalignant diseases in which AFP is elevated.

Subversion of immune system by tumor cells and role of prostaglandins

Abstract: Mice bearing syngeneic tumors, chemical and virus-induced, became immunologically unresponsive to sheep erythrocytes. The increase in the degree of unresponsiveness with tumor growth suggested a causal relationship. Immunosuppression was in fact caused by the tumor cells because the addition of tumor cells to in vitro cultures of spleen cells and sheep erythrocytes resulted in suppression of antibody response. Suppression was dose dependent with a ratio of 1 to 1000 of tumor cells to spleen cells sufficient to produce significant suppression. Prostaglandins were found to have a role in immunosuppression by tumor cells in that PGE2 was itself immunosuppressive and in that indomethacin and aspirin, inhibitors of prostaglandin synthetases, blocked immunosuppression in vitro and retarded tumor growth in vivo. These findings suggest that tumors, although antigenic, may be able to escape immuno-sureillance by their host by means of subverting the immune system. Thus, success of immunotherapy may well depend on our ability to prevent or block the immunosuppressive activity of tumors.

Enzymatic immunological method for the determination of antigens and antibodies

Abstract: The present invention relates to improvements in the sandwich technique for the determination of a component of an antigen-antibody reaction in a liquid sample to be tested, utilizing as reagents (a) one component of said reaction bound to the surface of a water-insoluble, water-insuspensible, solid carrier, and (b) a component having the same immunological properties covalently linked to an enzyme. The liquid sample is contacted and incubated with the reagent(s) to form a reaction mixture, the enzyme activity of either the liquid or solid phase of which is a measure of the presence and quantity of the component to be determined. The method is especially useful for diagnostic testing for hepatitis or rubella antibodies.

Changes in blood hormone levels during the immune response.

Abstract: Injection of three different antigens into rats or mice led in the course of several days to about a threefold increase in serum corticosterone levels and concommitantly to a decrease in thyroxine (rats). In view of the known immuno-suppressive effect of the glucocorticoids the possibility is considered that the endocrine changes induced during the immune response could significantly modulate the subsequent character of the immune response, e.i. magnitude, duration and lymphoid cell proliferation, however, a more complete pattern of hormonal variations and their cause needs to be established. These findings while admittedly preliminary, suffice to provide an indication of a temporal pattern of hormonal change during the immune response which could be important in immunoregulation.

Recognition by pregnancy serums of non-HL-A alloantigens selectively expressed on B lymphocytes.

Abstract: A group of alloantibodies are found in pregnancy sera which react with antigens present on B lymphocytes and monocytes but are not detectable on the vast majority of unstimulated T cells. This specificity distinguishes them from HL-A antibodies which react with both cell types. They were readily recognized through indirect fluorescent antibody analysis by employing the combination of B-cell lymphoid lines and normal peripheral blood T cells. Different sera gave a variety of patterns of reactivity with a panel of 11 lymphoid lines. Similar differential patterns were also observed with normal B cells from different individuals particularly after concentrating the B cells. The antibodies were also cytotoxic to B cells and this procedure gave parallel results to the fluorescence method. The pattern of reactions obtained indicated a very heterogeneous system similar to that for HL-A. Special study of certain of the sera provided evidence that the lymphocyte-defined determinants of the mixed lymphocyte reaction system were involved. For convenience the term HL-B has been employed for these antigens.

Antibody-forming cells in human colostrum after oral immunisation.

Abstract: IT has been suggested that feeding infants with human milk reduces the incidence of gastrointestinal infections1. Although macrophages, lymphocytes and antibodies in the milk are probably important in this protection2,3, the mechanism for the development of specific immunity to enteric pathogens is not known. Human colostral cells synthesise IgA (ref. 4), and we have used the haemolysis-in-gel technique to demonstrate that human colostrum contains numerous cells which produce IgA antibodies against the O antigens of commonly encountered Escherichia coli bacteria5. This suggested that the sensitised lymphocytes had either undergone antigen-induced clonal proliferation within the mammary gland or had homed to that organ from another site after becoming sensitised. Because of reports that gastrointestinal immunisation of germ-free mice led to local6 and systemic7 production of IgA antibodies, and that cells from Peyer's patches effectively repopulate the ileum of lethally-irradiated rabbits with IgA-producing cells8, we have examined the effect of gastrointestinal immunisation on the development of antibody-producing cells in colostrum of humans. We found that oral administration of a non-pathogenic strain of E. coli led to the rapid appearance of colostral cells producing antibodies against the O antigen of the organism.

Shared idiotypic determinants on B and T lymphocytes reactive against the same antigenic determinants. I. Demonstration of similar or identical idiotypes on IgG molecules and T-cell receptors with specificity for the same alloantigens.

Abstract: Antigen-binding receptors on T lymphocytes and IgG antibodies with the same antigen-binding specificity as the T-cell receptors display shared or identical idiotypes. This was shown using a system where adult F1 hybrid rats between two inbred strains were inoculated with T lymphocytes from one parental strain. Such F1 hybrid rats produce antibodies directed against idiotypic determinants present on IgG alloantibodies, produced in the T donor genotype strain and with specificity for the alloantigens of the other parental strain. The idiotypic nature of the F1 antialloantibody serum against the parental alloantibodies was demonstrated both by indirect hemagglutination tests or by gel diffusion using alloantisera with different specificity as targets. Furthermore, the F1 anti-T-lymphocyte sera could be shown to contain antibodies against idiotypic parental T lymphocytes as well. This was shown by the capacity of the antisera, in the presence of complement, to wipe out the relevant parental T-cell reactivity against the other parental strain (as measured in MLC or GVH) whilst leaving the T-lymphocyte reactivity against a third, unrelated allogeneic strain intact. These findings demonstrate that F1 hybrid rats inoculated with parental T lymphocytes make anti-idiotypic antibodies directed against both the T cell receptors and IgG alloantibodies of that parental strain with specificity for alloantigens of the other parental strain. In order to prove identity between the anti-idiotypic antibodies against the B and T-cell antigen-binding molecules the following experiments were carried out; highly purified IgG from relevant alloantibody-containing serum in immunosorbent from could be shown to selectively remove both anti-idiotypic activities from the F1 antiserum. Further more, parental normal T lymphocytes could be shown capable of removing from the anti-idiotypic antisera all those antibodies that would cause agglutination of the relevant alloantibody-coated erythrocytes in the indirect agglutination assay. We would thus conclude that T and B lymphocytes reactive against a given antigenic determinant use receptors with antigen-binding areas coded for by the same variable gene subset(s).