Genetic control of cytolytic t-lymphocyte responses. II. The role of the host genotype in parental leads to F1 radiation chimeras in the control of the specificity of cytolytic T-lymphocyte responses to trinitrophenyl-modified syngeneic cells.
01 Aug 1978-Journal of Experimental Medicine (The Rockefeller University Press)-Vol. 148, Iss: 2, pp 352-359
TL;DR: It is demonstrated that the host environment where T cells differentiate influences the specificity of the primary cytolytic T-lymphocyte (CTL) response to TNP-modified syngeneic antigens.
Abstract: Bone marrow cells from C3H (H-2k) mice, a strain that does not exhibit cross-reactive lysis of trinitrophenyl (TNP)-modified allogeneic targets, were allowed to mature in heavily irradiated (B6 times C3H)F1 (H-2b/k) recipients, an F1 hybrid that does demonstrate cross-reactive lysis. Spleen cells from these chimeric mice were removed after 3-4 mo and by H-2 typing shown to be of C3H origin. These cells were found to be tolerant to B6 alloantigens by mixed lymphocyte reaction and cell-mediated cytotoxicity and, when stimulated in vitro with TNP-modified syngeneic cells, now cross-reactively lysed TNP-modified allogeneic targets. These studies demonstrate that the host environment where T cells differentiate influences the specificity of the primary cytolytic T-lymphocyte (CTL) response to TNP-modified syngeneic antigens.
Citations
More filters
TL;DR: Complete Freund's adjuvant cyclophosphamide 2, 4-dinitro-l-fIuorobenzene delayed-type hypersensitivity fowl gamma globulin terpolymer L-glutamic acidso-L-alanineso- L-tyrosineio immunoglobulin intraperitoneal ly 5-(i26i)iodo-2'-deoxyuridine .
Abstract: complete Freund's adjuvant cyclophosphamide 2, 4-dinitro-l-fIuorobenzene delayed-type hypersensitivity fowl gamma globulin terpolymer L-glutamic acidso-L-alanineso-L-tyrosineio immunoglobulin intraperitoneal ly 5-(i26i)iodo-2'-deoxyuridine . keyhole limpet hemocyanin isoenzyme B of lactic dehydrogenasc low responder ratio of radioactivity of left to right car major histocompatibility complex macrophages responders standard errors cytotoxic T cells T cells involved in DTH helper T cells suppressor T cells poly-L-(Ty r.G I u)-poly-D,L-Ala—poly-L-Lys 2, 4, 6-trinitrophenyl
48 citations
TL;DR: The physiologic significance of hapten- and carrier-specific inducer T cells in the response to foreign antigens and autoantigens is discussed.
Abstract: Hapten-reactive inducer T cell clones can be divided into two groups based on their activation specificity. The first and largest group is conjugate specific. These clones are activated only by hapten coupled to the same carrier protein used for in vitro selection. The second group, which is quite rare, is hapten specific. Clones of this type are activated by hapten coupled to all foreign and autologus proteins tested. Both types of clones corecognize soluble antigen in association with products of the I-A locus. The hapten-specific cells were used to analyze the molecular basis of I-A vs. I-E gene control. The physiologic significance of hapten- and carrier-specific inducer T cells in the response to foreign antigens and autoantigens is discussed.
46 citations
Cites background from "Genetic control of cytolytic t-lymp..."
...Second, analyses of cell-mediated responses to TNP have indicated that inducer cells from H-2 b and H-2 d mice both respond to TNP-coupled I-A d cells, while inducer cells from mice expressing I-A k gene products do not (35, 36)....
[...]
01 Jan 1980
TL;DR: The discovery of Ir genes introduced an apparently new level of antigen recognition whose diversity and specificity had to be explained in addition to those of familiar immunoglobulins.
Abstract: The continuous and growing excitement elicited by the concept of immune response (Ir)* genes since their discovery in the mid-1960s (McDevitt and Benacerraf, 1969; Benacerraf and McDevitt, 1972; Benacerraf and Katz, 1975; Benacerraf and Germain, 1978) can be understood as soon as that concept is fully defined. Immune response genes are operationally defined as antigen-specific genes that control the ability of an animal to raise an i immune response, humoral or cellular, to a particular antigen. The antigen specificity is a crucial aspect of the definition. Thus genes that lead to broad immune deficiency diseases, such as Wiscott-Aldrich syndrome or ataxia telangiectasia in man (Waldmann et al., 1980) and the CBA/N defect in the mouse (Mosier et al., 1977), are excluded from the concept. However, the antigen specificity is also what leads to all the excitement. The hallmark of immunology has always been the exquisite, fine specificity of antigen recognition combined with the seemingly endless diversity of specificities that could be elicited. Despite many investigator years of research invested in trying to explain this diversity, primarily with regard to immunoglobulins, providing us with some understanding of the molecular bases of specificity (Kabat, 1978; Berzofsky and Schechter, 1980, and reviews cited therein), the mechanisms of generation of antibody diversity are still the subject of continuing controversy (Cunningham, 1976; Kabat et al., 1979; Seidman et al., 1979, and references cited therein). The discovery of Ir genes introduced an apparently new level of antigen recognition whose diversity and specificity had to be explained in addition to those of familiar immunoglobulins.
44 citations
TL;DR: The results demonstrate that congenic strains differing only in the MHC (B10.D2 and B10.BR) differ significantly in their H-2Kb-specific CTL repertoires, and indicate that MHC-specific tolerance cannot be solely responsible for repertiore differences between M HC-disparate strains.
Abstract: Superimposed on the heterogeneous anti-H-2Kb cytolytic T lymphocyte (CTL) receptor repertoire of allogeneic murine strains are reactivities that recur with high frequency amongst individuals of any given strain. These receptor specificities represent phenotypic markers of the CTL repertoire and, as such, have been used to compare receptor repertoires of genetically disparate strains. The results demonstrate that congenic strains differing only in the MHC (B10.D2 and B10.BR) differ significantly in their H-2Kb-specific CTL repertoires. This finding clearly demonstrates a role for the MHC in determination of the CTL precursor repertoire. The mechanism by which MHC influences CTL specificity was explored through analysis of the anti-H-2Kb repertoire of (B10.BR X B10.D2)F1 hybrids. Because at least one recurrent parental specificity has found to be recurrent in F1 progeny as well, the findings indicate that MHC-specific tolerance cannot be solely responsible for repertiore differences between MHC-disparate strains. In addition, the F1 repertoire is characterized by the emergence of several nonparental recurrent specificities.
31 citations
TL;DR: The spectrum of MHC-restricted effector function shown by mature T cells was considered to reflect physiological differentiation processes that were in some way dictated by radiation-resistant thymus epithelium (Zinkernagel 1978).
Abstract: The discovery of major histocompatibility complex (MHC) restriction of virusimmune cytotoxic T lyhiphocyte (CTL) function raised immediate questions about the nature of the T cell repertoire and, by association, the role of the thymus (Zinkernagel & Doherty 1974. Doherty & Zinkernagel 1975). Immunology had been primed for this response by Jerne's (1971) provocative proposal that the repertoire of lymphocyte specificities for foreign (non-MHC) antigens was derived, by somatic mutation, from the V-gene poo! coding tor recognition of the self MHC glycoproteins possessed by the individual. The thymus could thus be regarded as a mutant breeding organ for the generation of MHCrestricted precursor T cells, an argument which fitted well with the later 'altered self 'interaction antigen' hypotheses (Zinkernagel & Doherty 1974, Doherty & Zinkertiagel 1975, Doherty et al. 1976. Bevan 1977). The debate was focused on the thymus in a much more direct way when Zinkernagel (Zinkernagel et al. 1978b, Zinkernagel 1978) found that adult thymectomized (PI Xp2)Fi radiation chimeras, that had been reconstituted with (PiXP:)F| bone marrow cells and an irradiated Pi thymus graft, subsequently developed virus-immune CTL responses that were totally restricted to Pi. The spectrum of MHC-restricted effector function shown by mature T cells was considered to reflect physiological differentiation processes that were in some way dictated by radiation-resistant thymus epithelium (Zinkernagel 1978). This, together with the experiments of Bevan (Bevan 1977, Bevan & Fink 1978),
28 citations