THE PRESENTATION OF SELF AND ALLOGENEIC MHC PEPTIDES TO T-LYMPHOCYTES

The presentation of donor-derived MHC peptides by recipient APCs to T cells is an essential component of the rejection of allografts (indire ct allorecognition). Initial alloreactive T cell response is confined to a few well processed and presented dominant determinants on donor M HC. However, during long-term graft rejection, T cell response spreads to formerly poorly presented cryptic allogeneic MHC peptides. This ph enomenon is likely to play an important role in the amplification and the perpetuation of the rejection process. Additionally, we present ev idence that T cell repertoire selection to allogeneic MHC peptides is acquired via recognition of self-MHC peptides Presented in the thymus during ontogeny. Supporting this view, we have shown that indirect all oresponses can lead to self-T cell tolerance breakdown to cross-reacti ve determinants on self-MMC molecules or alternatively chat sensitizat ion of recipients to self-MHC peptides can lead to accelerated graft r ejection. It is therefore essential to dei ermine the factors which go vern the processing and presentation of self and allogeneic MHC molecu les and to elucidate the mechanisms regulating subsequent T cell respo nses in order to design antigen-specific based immune therapies in tra nsplantation. (C) American Society for Histocompatibility and Immunoge netics, 1998. Published by Elsevier Science Inc.