Responses to the H–2K^ba mutant involve recognition of syngeneic Ia molecules

Abstract

Conventional antigens appear to be recognized by T lymphocytes only when associated with major histocompatibility complex (MHC) antigens. Using antigen-specific proliferation as a model for helper T lymphocytes, it has been demonstrated that Ly1⁺ T cells recognize antigen presented in association with syngeneic la molecules^1,2. In contrast to responses to conventional antigens, however, a large number of studies have suggested that the stimulation of alloreactive Ly1⁺ T cells, and helper T cells specific for allogeneic cytotoxic T lymphocyte (CTL) responses, involve the direct recognition of Ia alloantigens^3–5. For the generation of optimal allogeneic CTL activity it has been proposed that Ly1⁺ T cells recognize allo-Ia antigens directly and provide help to pre-CTLs that respond to allo-H–2K and/or D determinants. Thus, the B6.C.H–2^bm1 mutant (bm1, formerly referred to as Hz1), which is believed to consist of a substitution of two amino acids in the H–2K^b antigen⁶, has presented a paradox, for it can stimulate strong mixed lymphocyte culture (MLC), graft versus host and CTL responses^7,8 by T cells of H–2^b haplotype mice in the apparent absence of any alloantigenic differences in the I region. We now present evidence that the stimulation of proliferative and helper T cells by the mutant B6.C.H–2^bm1 results from the H–2K^ba antigen being recognized in the context of syngeneic Ia determinants. Thus responses to both conventional antigens and allogeneic MHC gene products may proceed via the recognition of antigen in the context of self Ia molecules.