Secondary in vitro responses of T lymphocytes to non-H-2 alloantigens self-H-2-restricted responses induced in heterologous serum are not dependent on primary-stimulating non-H-2 alloantigens.

Abstract

The role of non-H-2 alloantigens, specifically Mls locus products, in secondary in vitro T[thymus-derived]-cell-mediated cytotoxicity was studied. Splenic T lymphocytes, activated against Mls locus alloantigens in primary-mixed cultures and isoalted by velocity sedimentation gradient separation techniques, were used as responding populations in secondary mixed leukocyte cultures (MLC) and cell-mediated lympholysis (CML). Such T-cell clones exhibited self-H-2-restricted or anti-Mls locus-specific reactivity, with this dichotomy of reactivity depending only on the primary culture conditins. Mls locus-activated T lymphocytes generated in cultures supplemented with homologous serum exhibited specific memory responses in MLC, yet remained incapable of effecting target cell destruction against Mls locus antigens or against self-H-2 structures in CML. Activated T-cell clones generated in the presence of heterologous serum displayed H-2-restricted reactivity in secondary MLC and CML. H-2-restricted MLC activation was controlled by H-2 I region products, whereas H-2-restricted CML activity was controlled by products of the H-2 serologically defined regions. Although heterologous serum was a necessary (and sufficient) entity for development of H-2-restricted responses, heterologous serum acts via modification of cell surface components.