Interaction between genes of chromosome 12 and I-region genes in the control of the arsonate-specific T cell repertoire.

Abstract

The T lymphocyte repertoire consists of clones recognizing foreign antigens together with self histocompatibility molecules. Diversification of the receptor is believed to arise by somatic mechanisms during ontogeny. MHC gene products are essential for this process as well as for antigen recognition and expression of T cell functions. Yet, the antigen-specific T cell receptor is not encoded by MHC genes. Little is still known concerning the nature and the genetic origin of this receptor despite numerous experimental approaches. Although the T cell repertoire is mainly determined, in a single individual, by the alleles expressed at the MHC locus, one can postulate that it could also be influenced by the existence of alleles of the germ line gene(s) encoding the T cell receptor. If so, an analysis of the T cell fine specificity in mice of the same H-2 haplotype with different background genes might permit the mapping of the genes coding for this receptor. Such an experimental approach requires the use of an antigen consisting of only one major determinant. Several recent observations suggested to us that the hapten p-azobenzenearsonate (ABA) was a suitable model for such investigations. Thus, we decided to compare the specific pattern of responses to ABA-tyrosine, ABA-histidine and to free ABA in different inbred mouse strains. We report here that the lymph node T cell proliferative response to these molecules is under the control of an ABA-specific Ir gene. The ABA-Tyr conjugate is the most potent immunogen of the three in vivo as well as in vitro. High responder strains to ABA-His or ABA are included in the group of high responders to ABA-Tyr suggesting that the response to the three molecules is under the control of the same Ir-gene. The pattern of the response is also influenced by background gene(s). One of these can be localized on chromosome 12 using congenic mice. No close linkage to IgCH markers or VH idiotypes can be demonstrated but a linkage of this gene(s) to the Pre-1 locus seems possible. B lymphocytes do not seem to account for the involvement of Chr.12-genes in the response since; in our experimental system, they do not present ABA to T cells nor do they proliferate in the assays. Similarly, ABA-Tyr-antibody complexes do not enhance macrophages presentation of ABA to T cells, which supports the conclusion that IgCH or VH gene products are not involved in the control of the response.(ABSTRACT TRUNCATED AT 400 WORDS)