Induction of T-cell response to cryptic MHC determinants during allograft rejection

The presentation of MHC peptides by recipient and donor antigen presenting cells is an essential element in allorecognition and allograft reject-ion. MHC proteins contains two sets of determinants: the dominant determinants that are efficiently processed and presented to T cells, and thr cryptic determinants that are not presented sufficiently enough to induce T-cell responses in vivo. In transplanted mice, initial T-cell response to MHC peptides is consistently limited to a single or a few immunodominant determinants on donor MHC molecule. However, in this article we show that under appropriate circumstances the hierarchy of determinants on MHC molecules can be disrupted. First, we observed that gamma IFN can trigger de novo presentation of cryptic self-MHC pep-tides by spleen cells. Moreover, we showed that allotransplantation is associated with induction of T-cell responses to formerly cryptic determinants on both syngeneic and allogeneic MHC molecules. Our results suggest thar cross-reactivity and inflammation are responsible for che initiation of these auto- and alloimmune responses after transplantation. (C) American Society for Histocompatibility and Immunogenetics, 2000. Published by Elsevier Science Inc.