Presentation and recognition of major and minor histocompatibility antigens

The structural basis of allorecognition is heterogeneous. For minor histocompatibility antigen-specific T cells and for a minority of anti-MHC T cells (indirect allorecognition), the allogeneic molecule acts as any other protein, and is processed and presented as a peptide in the context of self MHC. In circumstances where the MHC molecule is recognized unprocessed on the surface of the allogeneic cell, we have postulated that the factors important in recognition are determined by the relationship between the responder and stimulator MHC molecules. When the alloresponse is directed against an allogeneic molecule whose exposed surface closely resembles that of the responder homologue, the alloresponse can be regarded as resulting from mimicry of self MHC-restricted recognition of peptides which are differentially bound by responder and stimulator MHC molecules. When the alloantigen differs extensively in the MHC restriction-determining region of the molecule from the equivalent product in the responder, a chance high-affinity cross-reaction with the foreign MHC structure itself may be the most important mechanism.