CD4+ T cells are able to reject class I disparate allografts

The ability of CD4+ T cells to reject class I mismatched skin allografts remains controversial. In this study, we compare the ability of CD4+ T cells to reject class I disparate skin grafts differing by either a single class I allelic disparity or only 3 amino acids encoded by the H-2K locus. We demonstrate that skin grafts across a full H-2K allelic disparity, but not across a disparity of only three amino acids are efficiently rejected by CD4+ T cells. This observation is consistent with the possibility that peptides derived from allogeneic class I molecules generated through the major histocompatibility complex (MHC) class II antigen processing pathway can be recognized by host CD4 T cells and lead to rejection of class I mismatched skin grafts. The availability of peptides derived from allogeneic MHC class I molecules for presentation by host MHC class II may determine the efficiency of rejection of class I mismatched allografts by CD4+ T cells. Thus, class I mismatched allografts can be rejected by CD4+ T cells provided that host and donor MHC class I molecules are sufficiently disparate to activate CD4+ effectors.