Despite Biased TRBV Gene Usage against a Dominant HLA B57-Restricted Epitope, TCR Diversity Can Provide Recognition of Circulating Epitope Variants

• Published in: The Journal of immunology (1950) 2008-10, Vol.181 (7), p.5137-5146
• Main Authors: Simons, Brenna C, VanCompernolle, Scott E, Smith, Rita M, Wei, Jie, Barnett, Louise, Lorey, Shelly L, Meyer-Olson, Dirk, Kalams, Spyros A
• Format: Article
• Language: English
• Subjects: Antigen Presentation - genetics; Antigen Presentation - immunology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Chronic Disease; Clone Cells; Gene Rearrangement, beta-Chain T-Cell Antigen Receptor - genetics; Genetic Variation - immunology; HIV Core Protein p24 - blood; HIV Core Protein p24 - genetics; HIV Infections - immunology; HIV-1 - immunology; HIV-1 - pathogenicity; HLA-B Antigens - genetics; HLA-B Antigens - immunology; HLA-B Antigens - metabolism; Humans; Immunodominant Epitopes - blood; Immunodominant Epitopes - genetics; Immunodominant Epitopes - immunology; Immunoglobulin Variable Region - biosynthesis; Immunoglobulin Variable Region - blood; Immunoglobulin Variable Region - genetics; Protein Binding - genetics; Protein Binding - immunology; Receptors, Antigen, T-Cell, alpha-beta - blood; Receptors, Antigen, T-Cell, alpha-beta - genetics
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.181.7.5137

The role of epitope-specific TCR repertoire diversity in the control of HIV-1 viremia is unknown. Further analysis at the clonotype level is important for understanding the structural aspects of the HIV-1 specific repertoire that directly relate to CTL function and ability to suppress viral replication. In this study, we performed in-depth analysis of T cell clonotypes directed against a dominantly recognized HLA B57-restricted epitope (KAFSPEVIPMF; KF11) and identified common usage of the TCR beta-chain TRBV7 in eight of nine HLA B57 subjects examined, regardless of HLA B57 subtype. Despite this convergent TCR gene usage, structural and functional assays demonstrated no substantial difference in functional or structural avidity between TRBV7 and non-TRBV7 clonotypes and this epitopic peptide. In a subject where TRBV7-usage did not confer cross-reactivity against the dominant autologous sequence variant, another circulating TCR clonotype was able to preferentially recognize the variant peptide. These data demonstrate that despite selective recruitment of TCR for a conserved epitope over the course of chronic HIV-1 infection, TCR repertoire diversity may benefit the host through the ability to recognize circulating epitope variants.