Identification of Igh-C-linked determinants on suppressor T cell hybrids and factors specific for L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT).

Hyperimmunization of BALB/c mice with concanavalin A-stimulated blasts from the Ig allotype-congenic strain, C.B20, results in the production of antibodies reactive with T cells in an allotype-restricted manner. Spleen cells from these hyperimmune BALB/c mice were used to generate a panel of hybridomas that secrete monoclonal antibodies, reactive, in an allotype-restricted manner, exclusively with T cells subpopulations, and in particular, reactive with suppressor T cell hybridomas and their secreted soluble factors. Two functional classes of antibodies were identified: those that react with single polypeptide-chain suppressor T cell factors (TsF1) and the suppressor T cell hybridomas that produce such factors, and those that react with two polypeptide-chain suppressor T cell factors (TsF2) and their corresponding suppressor T cell hybridomas. These two classes of antibody were used to isolate molecules from the membranes of the respective suppressor T cell hybrids that are functionally and structurally related to the secreted suppressor T cell factors, suggesting a receptor function for these molecules.

The expression of anti-poly(LGlu60, LPhe40) idiotypic determinants dictated by the gene products in the major histocompatibility complex.

Antibodies raised in SWR/J mice (H-2q, Igc) to the random copolymer poly(LGlu60, LPhe40) (GPhe) were purified by immunoadsorbent chromatography and used to immunize a New Zealand red rabbit. The rabbit anti-idiotypic antiserum thus produced strongly inhibited the binding of 125I-GPhe by anti-GPhe antisera produced only in mice of H-2q haplotype, and had no effect on the binding of GPhe by anti-GPhe antisera produced in mice of other haplotypes, namely, H-2k and H-2p. The anti-idiotypic antiserum also inhibited the binding of GPhe by anti-GPhe-methylated bovine serum albumin antisera produced only in mice of H-2q haplotype. No linkage to Ig allotype was observed. The anti-GPhe antisera produced in F1 mice the anti-idiotypic antiserum demonstrating the dominant presence in these F1 mice of idiotypic determinants whose expression is dictated by the H-2q major histocompatibility complex (MHC). The anti-idiotypic antiserum also inhibited the binding of 125I-poly)LGlu56, LLys35, LPhe9) and 125I-GPhe antisera produced only in mice of H-2q haplotype. These specificities were also confirmed by the inhibition of the plaque-forming cells. It was concluded that the antibodies produced in mice of H-2q haplotype against GPhe and GLPhe share common idiotypic determinants that are recognized by the anti-idiotypic antiserum. A possible explanation for the unique findings that the expression of anti-GPhe idiotypic determinants in mice of H-2q haplotype are dictated by the gene product in the MHC is that the macrophages in mice of H-2q haplotype present unique determinants of GPhe polymer in the response process to GHphe.

Lymphoid function in F1 leads to parent chimeras: lack of evidence for adaptive differentiation of B cells or antigen-presenting cells.

Information was sought on whether B cells undergo abnormal differentiation in F1 leads to parent chimeras (irradiated parental-strain mice reconstituted with F1-hybrid bone marrow cells). As assessed by collaborative responses to sheep erythrocytes in vivo, three different types of T cells restricted to interaction with strain a H-2 determinants were shown to collaborate as effectively with heterologous F1 leads to b chimera B cells as with homologous F1 leads to a chimera B cells. This applied to both primed and unprimed B cells, to IgM- and IgG-antibody formation and to production of Ig allotype. Thus, unlike T cells, B cells from F1 leads to parent chimeras behaved indistinguishably from normal F1 B cells. F1 leads to parent chimeras were also examined for their capacity to present antigen to normal F1 T cells in vivo. The results suggested that the antigen-presenting cells in these chimeras were no different than in normal F1 mice. Collectively these data imply that, at least in the situation studied, raising F1 stem cells in a parental-strain environment has a marked effect on T-cell specificity but does not discernably influence the differentiation of B cells or macrophage-like cells.

Allotype-specific analysis of anti-(TYR,GLU)-ALA-LYS antibodies produced by Ir-1A high and low responder chimeric mice

Katz et al. (1) have demonstrated a restriction in lymphoid cell interaction when the antigen used is under immune response (Ir) gene control. T cells from (low responder x high responder) F(1) mice primed to the terpolymer L-glutamic acid, L-lysine, L-tyrosine (GLT) can collaborate with 2,4-dinitrophenyl (DNP)-primed B cells from the Ir-GLT high responder but not low responder strain in response to DNP-GLT (1). In contrast are the studies of Bechtol et al. and Bechtol and McDevitt (2,3), who examined the antibody responses of tetraparental mice immunized with the synthetic polypeptide poly-L(Tyr,Glu)-poly D,L-Ala- poly-L-Lys ((T,G)-A-L), an antigen under Ir-1A genetic control. Several tetraparental mice produced anti(T-,G)-A-L antibody of low responder strain immunoglobulin (Ig) allotype (2,3). These results indicated that he Ir-1A gene was not expressed in B cells and implied that interactions among genetically dissimilar cell populations could occur when tolerance existed to H-2 antigenic differences. Recent studies with bone marrow cell chimeric mice have shown that chimeric T cells can interact with H-2 histoincompatible B cells in response to antigens not under Ir gene control (4-6). To clarify whether lymphoid cell chimerism, with presumed tolerance to H-2 incompatibility, would permit effective cell interactions in response to antigens under Ir gene control, bone marrow cell chimeric mice were prepared by using strains differing both for Ig allotype and for high versus low responsiveness to (T,G)-A-L. An antigen-specific and allotype- specific antibody assay was used to discriminate the responses produced by high and low responder strain B cells in these chimeras. The results suggest that lymphoid cell chimerism per se is not sufficient to obviate Ir gene-mediated restriction in cell interaction.