DEGENERATE CYTOTOXIC T-CELL EPITOPES FROM PLASMODIUM-FALCIPARUM RESTRICTED BY MULTIPLE HLA-A AND HLA-B SUPERTYPE ALLELES

We recently described human leukocyte antigen (HLA) A2, A3 and B7 supe rtypes, characterized by largely overlapping peptide-binding specifici ties and represented in a high percentage of different populations. He re, we identified 17 Plasmodium falciparum peptides capable of binding these supertypes and assessed antigenicity in both vaccinated and nat urally exposed populations. Positive cytotoxic T lymphocyte recall and cytokine (interferon-gamma and tumor necrosis factor alpha) responses were detected for all peptides; all were recognized in the context of more than one HLA class I molecule; and at least 12 of the 17 were re cognized in the context of all HLA alleles studied. These data validat e the concept of HLA supertypes at the biological level, show that hig hly degenerate peptides are almost always recognized as epitopes, and demonstrate the feasibility of developing a universally effective vacc ine by focusing on a limited number of peptide specificities.