Cell-mediated cytotoxicity against allogeneic mutant H-2 antigens: Restricted and nonrestricted responses

Two 'gain and loss' type mutations of the H-2D region, the H-2^bm13 and H-2^bm14, resulted in the expression of noncross-reactive CML determinants that are unique to each mutation, the D^bm13 gains and D^bm14 gains, respectively. According to the results of direct cytolytic and competitive inhibition assays of in vitro induced primary cytotoxic T lymphocytes, allogeneic responses specific for D^bm13 gains are generated by responders bearing the H-2^b (K^bI^bD^b) haplotype, but not by responders bearing the H-2^bm14 (K^bI^bD^bm14), K^bI^bD(d), K^bI^b/(q)D(q) haplotype. Responses by the non-H-2^b responders against D^bm13 are limited to those determinants shared by the D^bm13 and D^b molecules. Because congenic mice differing only at the H-2D region are either responsive or nonresponsive to D^bm13 gains, the responsiveness is controlled by gene(s) in the H-2D region. F₁ hybrid offspring of responsive (H-2^b) and nonresponsive (non-H-2^b) parents are invariably responsive, indicating genetic dominance of the responsiveness. In contrast to the response against D^bm13 gains, cytotoxicity specific for D^bm14 gains is generated by responders bearing the H-2^b, H-2^bm13, K^bI^bD(d), K^bI^bD(k), or K^bI^b/(q)D(q) haplotype. These data indicate the existence of two types of allogeneic MHC determinants; one, represented by D^bm14 gains, is the classic type capable of eliciting CML responses in mice of a wide range of H-2 haplotypes, whereas the other, exemplified by D^bm13 gains, elicits CTL responses only in mice of a few related haplotypes. It is proposed that recogition of D^bm13 gains is restricted by structures shared by D^b and D^bm13 but missing from other D (or L, R, etc.) molecules, such as D^bm14, D(d), D(k), and D(q). Availability of various restricting structures in self MHC molecules may thus influence the alloreactive CTL repertoire.