Predicting population coverage of T-cell epitope-based diagnostics and vaccines |
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Authors: | Huynh-Hoa Bui John Sidney Kenny Dinh Scott Southwood Mark J Newman Alessandro Sette |
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Institution: | (1) Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, 3030 Bunker Hill Street, Suite 326, San Diego, CA 92109, USA;(2) IDM Inc., 5820 Nancy Ridge Drive, Suite 100, San Diego, CA 92121, USA |
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Abstract: | Background T cells recognize a complex between a specific major histocompatibility complex (MHC) molecule and a particular pathogen-derived
epitope. A given epitope will elicit a response only in individuals that express an MHC molecule capable of binding that particular
epitope. MHC molecules are extremely polymorphic and over a thousand different human MHC (HLA) alleles are known. A disproportionate
amount of MHC polymorphism occurs in positions constituting the peptide-binding region, and as a result, MHC molecules exhibit
a widely varying binding specificity. In the design of peptide-based vaccines and diagnostics, the issue of population coverage
in relation to MHC polymorphism is further complicated by the fact that different HLA types are expressed at dramatically
different frequencies in different ethnicities. Thus, without careful consideration, a vaccine or diagnostic with ethnically
biased population coverage could result. |
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Keywords: | |
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