Regulation of delayed type hypersensitivity : cellular and genetic requirements, with emphases on the response to histocompatibility antigens

The failure of successful exchange of tissues and organs between individuals of the same species is mainly due to the expression of histocompatibility (H) antigens on the cell surface of the transplanted tissues. Every individual has a unique set of genetically determined H-antigens. Gorer and Snell (1) found in their studies with inbred mouse strains that a single locus, situated on chromosome 17, controlled a cell surface antigen (which they called, antigen II) that elicited remarkable rapid allograft rejection. Snell (2) suggested that loci determining the fate of allografts should be referred to as histocompatibility antigens. The locus controling antigen II was called therefore histocompatibility antigen 2 locus or H-2 locus. Later studies (3, 4) showed that H-2 covered a cluster of loci. This complex of loci is called Major Histocompatibility Complex or MHC. Similar MHC's have been described in man (HLA complex) (5), in rat (Rt1 complex) (6), in dog (DLA complex) (7) and in several other vertebrates (8). Because of their capacity to induce rapid allograft rejection, the MHC coded antigens were called 'strong' or 'major' histocompatibility antigens and the antigens coded for by other loci were referred to as 'weak' or 'minor' histocompatibility (H) antigens (9). A striking quality of most MHCs is their polymorphism. The significance of this polymorphism is still a matter of speculations (1 0). The experiments described in this thesis deal with the regulation of the immune response of mice against H-antigens. Therefore the structure and function of the MHC of the mouse will be described in more detail.