Degenerate cytotoxic T cell epitopes from P. falciparum restricted by multiple HLA-A and HLA-B supertype alleles
D L Doolan, S L Hoffman, S Southwood, P A Wentworth, J Sidney, R W Chesnut, E Keogh, E Appella, T B Nutman, A A Lal, D M Gordon, A Oloo, A Sette, D L Doolan, S L Hoffman, S Southwood, P A Wentworth, J Sidney, R W Chesnut, E Keogh, E Appella, T B Nutman, A A Lal, D M Gordon, A Oloo, A Sette
Abstract
We recently described human leukocyte antigen (HLA) A2, A3 and B7 supertypes, characterized by largely overlapping peptide-binding specificities and represented in a high percentage of different populations. Here, we identified 17 Plasmodium falciparum peptides capable of binding these supertypes and assessed antigenicity in both vaccinated and naturally 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 recognized in the context of all HLA alleles studied. These data validate the concept of HLA supertypes at the biological level, show that highly degenerate peptides are almost always recognized as epitopes, and demonstrate the feasibility of developing a universally effective vaccine by focusing on a limited number of peptide specificities.
Source: PubMed