HLA-derived peptides as novel immunotherapeutics.

Soluble forms of HLA may be natural immunoregulatory molecules and may explain the "transfusion effect" seen in transplant patients in the precyclosporine era. Synthetic peptides corresponding to short linear sequences of HLA molecules have inhibitory effects on human T lymphocytes in vitro and cause tolerance induction in a rat heterotopic heart transplant model. Recent studies indicate that a subset of these peptides causes an increase in intracellular calcium which appears to account for T cell unresponsiveness and tolerance induction. The peptides bind to members of the heat-shock protein 70 family in a specific manner, depending upon peptide sequence. These studies provide a mechanism to explain the biologic activities of these new immunotherapeutic reagents.