Role of major histocompatibility complex gene products in delayed-type hypersensitivity

Abstract

Sensitized thymus-derived (T) lymphocytes can transfer delayed-type hypersensitivity (DTH) to naive mice only if there is identity at the major histocompatibility complex (MHC). The MHC region responsible differs according to the antigen used for sensitization. For transfer of DTH to fowl gamma globulin identity at I-A is necessary; for dinitrofluorobenzene, however, identity at either K, D, or I region is sufficient. T cells of one genotype, sensitized in a chimeric environment, transferred DTH to both parental strains even though these were MHC incompatible. However T cells from F1 hybrid mice, sensitized not in the F1 but in one parental strain, transferred DTH only to that parental strain, not to the other, in contrast to F1 T cells sensitized in the F1 which could transfer DTH to both parental strains. Macrophages pulsed with antigen in vitro could be used to sensitize syngeneic or semi-allogeneic mice for the transfer of DTH. Transfer was, however, successful only in the strain syngeneic to that from which the macrophages were derived. Evidence is also presented that genetically low-responder mice can be made to exhibit DTH provided they are pretreated with cyclophosphamide two days before sensitization. When considered in toto these results strongly argue in favor of the notion that there are receptors on activated T cells which recognize antigenic determinants and MHC gene products. The implications of these findings are discussed in relation to the role of macrophages in antigen presentation and to the possible parallel evolution of MHC gene products and of T cell receptors for antigen.