Persistent survival of prevalent clonotypes within an immunodominant HIV gag-specific CD8+ T cell response.

Abstract

CD8(+) T cells play a significant role in the control of HIV replication, yet the associated qualitative and quantitative factors that determine the outcome of infection remain obscure. In this study, we examined Ag-specific CD8(+) TCR repertoires longitudinally in a cohort of HLA-B*2705(+) long-term nonprogressors with chronic HIV-1 infection using a combination of molecular clonotype analysis and polychromatic flow cytometry. In each case, CD8(+) T cell populations specific for the immunodominant p24 Gag epitope KRWIILGLNK (KK10; residues 263-272) and naturally occurring variants thereof, restricted by HLA-B*2705, were studied at multiple time points; in addition, comparative data were collected for CD8(+) T cell populations specific for the CMV pp65 epitope NLVPMVATV (NV9; residues 495-503), restricted by HLA-A*0201. Dominant KK10-specific clonotypes persisted for several years and exhibited greater stability than their contemporaneous NV9-specific counterparts. Furthermore, these dominant KK10-specific clonotypes exhibited cross-reactivity with antigenic variants and expressed significantly higher levels of CD127 (IL-7Rα) and Bcl-2. Of note, we also found evidence that promiscuous TCR α-chain pairing associated with alterations in fine specificity for KK10 variants could contribute to TCR β-chain prevalence. Taken together, these data suggest that an antiapoptotic phenotype and the ability to cross-recognize variant epitopes contribute to clonotype longevity and selection within the peripheral memory T cell pool in the presence of persistent infection with a genetically unstable virus.

• Authors: David J van Bockel, David A Price, Mee Ling Munier, Vanessa Venturi, Tedi E Asher, Kristin Ladell, Hui Yee Greenaway, John Zaunders, Daniel C Douek, David A Cooper, Miles P Davenport, Anthony D Kelleher
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 186 Issue 1 Pg. 359-71 (Jan 01 2011) ISSN: 1550-6606 [Electronic] United States
• PMID: 21135165 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• Epitopes, T-Lymphocyte
• Immunodominant Epitopes
• gag Gene Products, Human Immunodeficiency Virus

Topics

• Amino Acid Sequence
• Antigen Presentation (immunology)
• Antigenic Variation (immunology)
• Apoptosis (immunology)
• CD8-Positive T-Lymphocytes (immunology, pathology, virology)
• Cell Separation
• Cell Survival (immunology)
• Clone Cells
• Epitopes, T-Lymphocyte (immunology, metabolism)
• Flow Cytometry
• HIV Infections (immunology, pathology, virology)
• HIV-1 (immunology)
• Humans
• Immune Evasion (immunology)
• Immunodominant Epitopes (immunology)
• Molecular Sequence Data
• Phenotype
• Prevalence
• gag Gene Products, Human Immunodeficiency Virus (immunology)