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 lymphoc ytes in vitro and cause tolerance induction in a rat heterotopic heart transplant model. Recent studies indicate that a subset of these pept ides causes an increase in intracellular calcium which appears to acco unt for T cell unresponsiveness and tolerance induction. The peptides bind to members of the heat-shock protein 70 family in a specific mann er, depending upon peptide sequence. These studies provide a mechanism to explain the biologic activities of these new immunotherapeutic rea gents. (C) 1996 Academic Press, Inc.