Antibody

About: Antibody is a research topic. Over the lifetime, 113941 publications have been published within this topic receiving 4130181 citations. The topic is also known as: Ab & antibodies.

Antisera and monoclonal antibodies specific for epitopes generated during oxidative modification of low density lipoprotein.

Abstract: Increasing evidence indicates that low density lipoprotein (LDL) has to be modified to induce foam cell formation. One such modification, oxidation of LDL, generates a number of highly reactive short chain-length aldehydic fragments of oxidized fatty acids capable of conjugating with lysine residues of apoprotein B. By immunizing animals with homologous malondialdehyde-modified LDL (MDA-LDL), 4-hydroxynonenal-LDL (4-HNE-LDL), and Cu+(+)-oxidized LDL, we developed polyvalent and monoclonal antibodies against three epitopes found in oxidatively modified LDL. The present article characterizes an antiserum and monoclonal antibody (MAL-2 and MDA2, respectively) specific for MDA-lysine, and an antiserum and monoclonal antibody (HNE-6 and NA59, respectively) specific for 4-HNE-lysine. In addition, a monoclonal antibody (OLF4-3C10) was developed against an as yet undefined epitope generated during Cu++ oxidation of LDL. With these antibodies, we demonstrated that MDA-lysine and 4-HNE-lysine adducts develop on apo-lipoprotein B during copper-induced oxidation of LDL in vitro. The application of these antibodies for immunocytochemical demonstration of oxidized lipoproteins in atherosclerotic lesions of progressive severity is described in the companion article. These antibodies should prove useful in studying the role of oxidatively modified lipoproteins as well as other oxidatively modified proteins in atherogenesis.

The natural-selection theory of antibody formation.

Abstract: An immense amount of experimental data related to the problem of antibody formation has accumulated. Theories offering a basic interpretation of these observations have, in contrast, been few. The theory formulated in the present paper, though highly speculative, attempts to provide a framework for the interpretation of the main features of antibody appearance in response to the injection of antigen into an animal. Two views concerning the mechanism of antibody formation are at present most widely favored. One is the "antigen-template" theory, developed by Breinl [1], Haurowitz [1,2], Mudd [3], Alexander [4], and Pauling [5]. This theory assumes that antibodies can be produced only by cells in which the antigen is present. The specific affinity of an antibody molecule toward the antigen is due to a complementarity in structure derived from the folding of part of the polypeptide chain of a globulin molecule in direct contact with a determinant or haptenic region of the antigen. The antigen thus serves as a template in the final stage of formation of a globulin molecule. The other view tries to establish a similarity between antibody formation and adaptive enzyme formation and allows for the continued production of antibody after the antigen has disappeared from the body. This is the "modified-enzyme" theory, formulated by Burnet [6,7] and Fenner [7]. They propose that the introduction of an antigen into cells, containing enzymes directed toward the disposal of effete cells and cellular debris from the organism itself, induces the formation of "enzymic units" adapted toward the destruction of the antigen. A renewed contact with the antigen stimulates the replication of these enzymic units. Circulating antibody molecules are partial replicas of the modified enzymic units, carrying specificity but lacking enzymic action. The "natural-selection" theory, proposed in the present paper, may be stated as follows: The role of the antigen is neither that of a template nor that of an enzyme modifier. The antigen is solely a selective carrier of spontaneously circulating antibody to a system of cells which can reproduce this antibody. Globulin molecules are continuously being synthesized in an enormous variety of different configurations. Among the population of circulating globulin molecules there will, spontaneously, be fractions possessing affinity toward any antigen to which the animal can respond. These are the so-called "natural" antibodies. The introduction of an antigen into the blood or into the lymph leads to the selective attachment to the antigen surface of those globulin molecules which happen to have a complementary configuration. The antigen carrying these molecules may then be engulfed by a phagocytic cell. When the globulin molecules thus brought into a cell have been dissociated from the surface of the antigen, the antigen has accomplished its role and can be eliminated.

Antibodies that inhibit fusion of human immunodeficiency virus-infected cells bind a 24-amino acid sequence of the viral envelope, gp120.

Abstract: Antisera to recombinant human immunodeficiency virus (HIV) proteins containing the entire envelope, gp160, or the central portion of the envelope, PB1, can inhibit fusion of virally infected cells in culture. This fusion inhibition is HIV-variant specific--that is, anti-gp160-IIIB inhibits fusion of isolate HTLV-IIIB-infected cells but not of isolate HTLV-IIIRF-infected cells. Both anti-gp160 and anti-PB1 are completely blocked in fusion inhibition activity by the addition of PB1 protein. A 24-amino acid peptide (RP135, amino acids 307-330) completely blocks fusion inhibition activity of both antisera and also blocks the activity of serum from a chimpanzee infected with HTLV-IIIB. Thus, the principal epitope that elicits fusion-inhibiting antibodies is located in the central portion of gp120.

Memory CD8+ T Cells Are Required for Protection from Persistent Hepatitis C Virus Infection

Abstract: Few hepatitis C virus (HCV) infections resolve spontaneously but those that do appear to afford protective immunity. Second infections are usually shorter in duration and are less likely to persist but mechanisms of virus control in immune individuals have not been identified. In this study we investigated whether memory helper and/or cytotoxic T lymphocytes provide protection in chimpanzees serially reinfected with the virus. Clearance of the first infection took 3–4 mo and coincided with the delayed onset of CD4+ and CD8+ T cell responses. High frequencies of memory T cells targeting multiple HCV proteins were stable over 7 yr of follow-up. Animals were infected for a second time to assess the protective role of memory T cells. In contrast to the prolonged course of the first infection, viremia was terminated within 14 d. Control of this second infection was kinetically linked to rapid acquisition of virus-specific cytolytic activity by liver resident CD8+ T cells and expansion of memory CD4+ and CD8+ T cells in blood. The importance of memory CD8+ T cells in control of HCV infection was confirmed by antibody-mediated depletion of this lymphocyte subset before a third infection. Virus replication was prolonged despite the presence of memory CD4+ T helper cells primed by the two prior infections and was not terminated until HCV-specific CD8+ T cells recovered in the liver. These experiments demonstrate an essential role for memory CD8+ T cells in long-term protection from chronic hepatitis C.

Identification of Ia glycoproteins in rat thymus and purification from rat spleen.

Abstract: A fraction of la-like glycoproteins was prepared from rat thymocytes by lentil lectin affinity chromatography and gel filtration in deoxycholate. Spleen cells from mice immunized with this preparation were fused with myeloma cells to produce antibody-secreting hybrid cell lines. Antibody from four lines called MRC OX, 3, 4, 5, 6 reacted with the la-like glycoproteins, and MRC OX 3 antibody recognized an antigenie determinant polymorphic in the rat. All four antibodies also bound to mouse spleen cells and all detected polymorphisms. Studies on recombinant mouse strains suggest that the determinants are coded by the I-A subregion of the H-2 complex. MRC OX 3 correlates with Ia specificity 9, while MRC OX 4, 5, 6 correlate with specificity 17 or 18. MRC OX 4 monoclonal antibody was used for affinity chromatography to purify Ia glycoproteins from rat spleen. The rat Ia glycoprotein complex was composed of two noncovalently linked polypeptide chains of apparent mol. wt. (unreduced) 30 000 and 24 000 as determined by polyacrylamide gel electrophoresis in sodium dodecyl sulfate. The purified Ia glycoprotein partially inhibited the binding to thoracic duct lymphocytes of an alloantiserum which detects Ia antigens linked to the major histocompatibility complex. The monoclonal anti-la antibodies bound to the majority of peripheral B lymphocytes and 18% of thymocytes, but did not significantly bind to peripheral T lymphocytes. There were on average 150000 molecules of Ia glycoprotein per la-positive B lymphocyte, and 45 000 molecules per la-positive thymocyte. From the same fusion, another cell line was prepared called MRC OX 2 which secretes monoclonal antibody to a previously undefined thymus glycoprotein of apparent mol. wt. 60000. Preliminary studies showed that the antigen was expressed on all thymocytes and on peripheral B lymphocytes in smaller amounts. It was also present in brain, but not liver or kidney homogenate.