Are allogeneic and associative recognition coincident T cell paradigms?

T lymphocytes are obsessed with cell surface molecules encoded by genes of the MHC, particularly class I (K/D) gene products. In one paradigm, T cells recognize and are activated by allodisparate class I antigens (allogeneic recognition); in another paradigm, T lymphocytes recognize viral antigens or haptens in the context of syngeneic class I determinants (associative recognition). Whether these paradigms are coincident, or even overlapping, is unresolved. We have studied neonatal tolerance induction among the H-2K^b parent strain and several of its class I mutants as a means of analyzing the fine discrimination potential of T cell recognition. Neonatal C57BL/6 animals were rendered tolerant of K^b mutant antigens; bm1, bm3, bm5, or bm8. Similar panels of mutant mice were rendered tolerant neonatally of the parent K^b antigen. When fully tolerant, mature animals were challenged with third-party grafts bearing related K^b alloantigenic disparities, they proved to be highly discriminant. K^b animals tolerant of bm1 or bm3 always rejected third-party grafts bearing bm3 and bm1 antigens, respectively. Similarly, the majority of K^b animals tolerant of bm5 or bm8 (and vice versa) were able to distinguish accurately the tolerated antigen from third-party antigens, rejecting grafts bearing the latter. Since associative recognition involving these antigens has been found to be at least partially degenerate and since neonatally tolerant animals nonetheless remain highly discriminant of these same antigenic variations, it is tempting to conclude that associative and allogeneic recognition address different aspects of T cell function.