Involvement of major histocompatibility complex products in tolerance induction in the thymus.

Abstract

KJ23a+ T cell clones, which bear the determinant encoded by the V beta 17a T cell receptor gene segment, frequently recognize IE molecules of various murine H-2 haplotypes. In the presence of IE molecules, thymic maturation of KJ23a+ clones is infrequent. We investigated the basis of this phenomenon by blocking expression of IE molecules with monoclonal anti-IE antibodies in organ cultures of fetal thymus and in neonates from the C57BR/cdJ strain (H-2k, V beta 17a homozygous). Our data support the contention that this process results from deletion of clones with anti-IE reactivity, as functional blocking of the IE molecule results in maturation of IE-reactive clones and increased numbers of KJ23a+ mature cells. In addition, we noted that blocking of functional IE expression in this haplotype permitted development of both CD4+/KJ23a+ and CD8+/KJ23a+ T cells. The CD4+ clones isolated from anti-IE-treated animals were frequently reactive against IEk; we could demonstrate no alloreactivity against B cell or B lymphoma stimulators in the CD4- clones. We conclude that clonal deletion events during thymic development may be initiated by T cell precursor interactions with MHC molecules against which the mature clones display no measurable reactivity. Specifically, clones destined to be MHC Class I-reactive may be deleted during development by interactions with MHC Class II molecules.