Degenerate cytotoxic T cell epitopes from P. falciparum restricted by multiple HLA-A and HLA-B supertype alleles

Doolan, Denise L., Hoffman, Stephen L., Southwood, Scott, Wentworth, Peggy A., Sidney, John, Chesnut, Robert W., Keogh, Elissa, Appella, Ettore, Nutman, Thomas B., Lal, Altaf A., Gordon, Daniel M., Oloo, Aggrey, and Sette, Alessandro (1997) Degenerate cytotoxic T cell epitopes from P. falciparum restricted by multiple HLA-A and HLA-B supertype alleles. Immunity, 7 (1). pp. 97-112.

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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-γ and tumor necrosis factor α) 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.

Item ID: 42773
Item Type: Article (Research - C1)
ISSN: 1097-4180
Funders: Naval Medical Research and Development Command (NMRDC), National Institute of Allergy and Infectious Disease (NIAID)
Projects and Grants: NMRDC Work Unit No. 63002AA0101HFX.1433, NMRDC Work Unit No. 62787A00101EFX.1432, NMRDC Work Unit No. 61102A.00101-BFX, NIAID-NIH contract N01-A1-45241
Date Deposited: 14 Sep 2016 03:18
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110799 Immunology not elsewhere classified @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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