Mixed lymphocyte reactivity and cell-mediated lympholysis to D-end differences of the murine major histocompatibility complex. Comparison of in vitro responses to exclusive D-end or more extensive MHC differences

Abstract

In vitro mixed lymphocyte culture (MLC) responses and the in vitro induction of cell-mediated lympholysis (CML) were studied in congenic strain combinations in which the responding and stimulating strains differed either at the entire major histocompatibility complex (MHC) or only at the D end of the MHC. In contrast to previously reported studies, the relative strengths of stimulation by 'D end only' differences or by whole MHC differences were examined by stimulating identical responding populations with titrated numbers of stimulating cells that differed from the responder either at the D end only or over the entire MHC. When tested in this manner isolated D-end differences were sufficient to generate significant MLC and CML responses in each combination tested. Several 'D end only' differences (the responses of B10.A to B10.A(2R); of B10.A(2R) to B10.A; of B10.D2 to B10.HTG; and of B10.HTG to B10.D2 were several fold less efficient in stimulating MLC and CML responses than were control stimulating cells differing over the whole MHC. In contrast, when the mutant D-end allele da was present on the stimulating cell (the responses of B10.D2 to B10.D2(M504) and of B10 to B10.D2(R106)), stimulation by an isolated D-end difference was comparable to stimulation by broader MHC differences. These findings are discussed in terms of the possible functional complexity of the D region.