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

• DOI: 10.1128/jvi.78.5.2187-2200.2004
• Publication Date: 2004-02-12T19:04:13Z
• Authors: Nicole Frahm; B. T. Korber; C. M. Adams; J. J. Szinger; R. Draenert; M. M. Addo; M. E. Feeney; K. Yusim; K. Sango; N. V. Brown; D. SenGupta; A. Piechocka-Trocha; T. Simonis; F. M. Marincola; A. G. Wurcel; D. R. Stone; C. J. Russell; P. Adolf; D. Cohen; T. Roach; A. StJohn; A. Khatri; K. Davis; J. Mullins; P. J. R. Goulder; B. D. Walker; C. Brander
• Keywords: CTL*; HIV vaccine

ABSTRACT 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 vivo, only scarce CTL data are available for ethnic populations currently most affected by epidemic. In this study, we examined CD8 + -T-cell African-American, Caucasian, Hispanic, and Caribbean which clade B dominates analyzed potential factors influencing immune recognition. Total HIV-specific were determined enzyme-linked immunospot assays 150 HIV-infected individuals using a consensus sequence peptide set spanning all HIV proteins. A total 88% 410 tested peptides recognized, Nef- Gag-specific dominated response each ethnicity terms both breadth magnitude. Three dominantly targeted regions within these proteins recognized >90% identified. Overall, magnitude correlated with individuals' CD4 counts but not viral loads. The frequency recognition was highly relative conservation sequence, presence predicted immunoproteasomal cleavage sites C-terminal half peptide, reduced amino acids impair binding optimal epitopes to restricting class I molecules. present study thus identifies contribute immunogenicity relatively conserved sequences may represent promising vaccine candidates ethnically heterogeneous populations.