A novel approach to the analysis of specificity, clonality, and frequency of HIV-specific T cell responses reveals a potential mechanism for control of viral escape

Daniel C. Douek, Michael R. Betts, Jason M. Brenchley, Brenna J. Hill, David R. Ambrozak, Ka Leung Ngai, Nitin J. Karandikar, Joseph P. Casazza, Richard A. Koup

Research output: Contribution to journalArticle

180 Scopus citations

Abstract

Escape from the CD8+ T cell response through epitope mutations can lead to loss of immune control of HIV replication. Theoretically, escape from CD8+ T cell recognition is less likely when multiple TCRs target individual MHC/peptide complexes, thereby increasing the chance that amino acid changes in the epitope could be tolerated. We studied the CD8+ T cell response to six immunodominant epitopes in five HIV-infected subjects using a novel approach combining peptide stimulation, cell surface cytokine capture, flow cytometric sorting, anchored RT-PCR, and real-time quantitative clonotypic TCR tracking. We found marked variability in the number of clonotypes targeting individual epitopes. One subject recognized a single epitope with six clonotypes, most of which were able to recognize and lyse cells expressing a major epitope variant that arose. Additionally, multiple clonotypes remained expanded during the course of infection, irrespective of epitope variant frequency. Thus, CD8+ T cells comprising multiple TCR clonotypes may expand in vivo in response to individual epitopes, and may increase the ability of the response to recognize virus escape mutants.

Original languageEnglish (US)
Pages (from-to)3099-3104
Number of pages6
JournalJournal of Immunology
Volume168
Issue number6
DOIs
StatePublished - Mar 15 2002

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Douek, D. C., Betts, M. R., Brenchley, J. M., Hill, B. J., Ambrozak, D. R., Ngai, K. L., Karandikar, N. J., Casazza, J. P., & Koup, R. A. (2002). A novel approach to the analysis of specificity, clonality, and frequency of HIV-specific T cell responses reveals a potential mechanism for control of viral escape. Journal of Immunology, 168(6), 3099-3104. https://doi.org/10.4049/jimmunol.168.6.3099