TCR contact residue hydrophobicity is a hallmark of…接触残留物疏水性是的标志.pdfVIP

TCR contact residue hydrophobicity is a hallmark of immunogenic CD8+ T cell epitopes a,b,1 b,c,1 d d e e e Diego Chowell , Sri Krishna , Pablo D. Becker , Clément Cocita , Jack Shu , Xuefang Tan , Philip D. Greenberg , Linda S. Klavinskisd,2, Joseph N. Blattmanf,2, and Karen S. Andersonb,2 aSimon A. Levin Mathematical, Computational, and Modeling Sciences Center, bCenter for Personalized Diagnostics, and cSchool of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ 85287; dDepartment of Immunobiology, King’s College London, London SE1 9RT, United Kingdom; eDepartment of Immunology, University of Washington, Seattle, WA 98195; and fCenter for Infectious Diseases and Vaccinology, Arizona State University, Tempe, AZ 85287 Edited by Ira Mellman, Genentech, Inc., South San Francisco, CA, and approved March 2, 2015 (received for review January 21, 2015) Despite the availability of major histocompatibility complex (MHC)- confirmation of MHC-bound peptides, and scarcity of experimen- binding peptide prediction algorithms, the development of T-cell tally confirmed immunogenic epitopes within the infectious and self vaccines against pathogen and tumor antigens remains challenged proteome (4). As a result, T-cell epitope prediction algorithms have by inefficient identification of immunogenic epitopes. CD8+ T cells focused on amino acid binding affinity for specific MHC motifs must distinguish immunogenic epitopes from nonimmunogenic self and the protein’s proteasomal cleavage pattern to identify candi- peptides to respond effectively against an antigen without endan- date T-cell epitopes (11–14). gering the viability of the