Consistent Cytotoxic-T-Lymphocyte Targeting of Immunodominant Regions in Human Immunodeficiency Virus across Multiple Ethnicities

作者：Nicole Frahm, Bette Korber, Craig Adams, James Szinger, Rika Draenert, Marylyn M. Addo, Margaret E. Feeney, Karina Yusim, Kaori Sango, Nancy V. Brown, Devi SenGupta, Alicja Piechocka‐Trocha, Toni B. Simonis, Franco Marincola, Alysse G. Wurcel, David R. Stone, Christopher J. Russell, P. Adolf, Dani Cohen, Timothy Roach, A. StJohn, Ashok Khatri, Katie L. Davis, James I. Mullins, Philip Goulder, Bruce D. Walker, Christian Brander · 发表于：Journal of Virology · 年份：2004 · DOI：10.1128/jvi.78.5.2187-2200.2004 · 被引用次数：276 · 研究领域：HIV Research and Treatment、vaccines and immunoinformatics approaches、HIV/AIDS drug development and treatment

Although there is increasing evidence that virus-specific cytotoxic-T-lymphocyte (CTL) responses play an important role in the control of human immunodeficiency virus (HIV) replication in vivo, only scarce CTL data are available for the ethnic populations currently most affected by the epidemic. In this study, we examined the CD8(+)-T-cell responses in African-American, Caucasian, Hispanic, and Caribbean populations in which clade B virus dominates and analyzed the potential factors influencing immune recognition. Total HIV-specific CD8(+)-T-cell responses were determined by enzyme-linked immunospot assays in 150 HIV-infected individuals by using a clade B consensus sequence peptide set spanning all HIV proteins. A total of 88% of the 410 tested peptides were recognized, and Nef- and Gag-specific responses dominated the total response for each ethnicity in terms of both breadth and magnitude. Three dominantly targeted regions within these proteins that were recognized by >90% of individuals in each ethnicity were identified. Overall, the total breadth and magnitude of CD8(+)-T-cell responses correlated with individuals' CD4 counts but not with viral loads. The frequency of recognition for each peptide was highly correlated with the relative conservation of the peptide sequence, the presence of predicted immunoproteasomal cleavage sites within the C-terminal half of the peptide, and a reduced frequency of amino acids that impair binding of optimal epitopes to the restricting c...