Immunologic characterization of MHC recombinant swine: role of class I and II antigens in in vitro immune responses.

A recombinant haplotype between the class I and class II major histocompatibility loci of inbred miniature swine has made it possible to study the role of the corresponding antigens in in vitro and in vivo immune responses. Before examining the effects of selective SLA locus matching on allograft survival, it was deemed necessary to determine the corresponding effects on in vitro parameters of immunity. The results presented in this paper indicate that: (1) a difference at the class II loci was required for a maximal proliferative response; (2) class I antigen differences alone led to a slight proliferative response which depended on the haplotype combination used; (3) in cell-mediated cytoxicity assays, the class I antigens were found to be the primary targets for lysis. Although optimal CTL generation required the presence of both class I and class II antigen differences, CTL were sometimes generated in the absence of a known class II difference. The weak, intermittent cytotoxicity seen in these cultures of class II matched cells could be augmented by the addition of third party, class I matched, class II mismatched, stimulator cells. Taken together, these data provide evidence for the conservation of function of antigen class between species. They also provide further evidence for the two-signal hypothesis of CTL generation. Thus, MHC recombinant swine provide a model for the study of the effect of antigen class on in vitro and in vivo immunobiology.