Iat epitopes on T cell receptor for self MHC class II determinants

Abstract

Anti-Iatk monoclonal antibodies (mAbs) were found to inhibit syngeneic mixed lymphocyte reaction (SMLR) of mice with k and a haplotypes (H-2k and H-2a) of the major histocompatibility complex (MHC) by acting on responder T cells but not stimulator cells. Only the early phase of SMLR was inhibited by anti-Iat mAbs. The inhibitory effect was due to the blocking of autoreactive T cells but not induction of suppressor lymphocytes. Cross-linking of Iat epitopes induced T cell proliferation of k haplotype strain. The inhibitory pattern of SMLR by four anti-Iat mAbs varied among different strains of mice. The inhibitory pattern seemed to depend on MHC and unidentified non-MHC background genes possessed by stimulator cells, suggesting that the shape of the MHC recognition site must have different conformation depending on both MHC and non-MHC gene products recognized. However, the inhibitory pattern of SMLR by anti-Iat mAbs of strains which differ at the I-J locus: B10.A(5R) and B10.A(3R) was dependent on the genotype of stimulator cells. The same was observed in B10.S(9R) and B10.HTT strains. The inhibitory activity of anti-Iat mAbs was entirely directed against responder T cells and was not passively carried out by the stimulators. It was concluded that Iat epitopes are I region controlled determinants that are utilized by T cells as receptors for self Ia antigens. It is suggested that anti-Iat mAbs react with an idiotype on the receptor(s) for Ia or I-J, or possibly a "receptor" for these receptors.