HLA-derived peptides as a strategy for the prevention of allograft rejection

Synthetic peptides corresponding to linear sequences of HLA molecules are potent immune modulators both in vitro and in vivo. Peptides corresponding to sequences of selected alpha helices of HLA class I molecules induce immunologic tolerance in animal models and have been shown to be non- toxic in Phase I clinical trials. Preliminary data from Phase II trials indicate that these peptides block cell-mediated cytotoxicity in humans. Like the immunosuppressive desoxyspergualin, these peptides bind to heat shock protein 70 family members. Peptides corresponding to analogous regions of HLA class II molecules similarly inhibit transplant rejection and autoimmune models in vivo but do not bind to heat shock proteins. Clinical trials with these peptides are not yet underway. These studies suggest that linear sequences of HLA molecules may be physiological immune modulators and that synthetic peptides corresponding to linear sequences of HLA molecules may be useful for therapy of transplantation and a myriad of other immune-mediated diseases.