Clonotypic structure of the human CD4+ memory T cell response to cytomegalovirus

A. D. Bitmansour, S. L. Waldrop, C. J. Pitcher, E. Khatamzas, F. Kern, V. C. Maino, L. J. Picker

Research output: Contribution to journalArticle

88 Scopus citations

Abstract

High steady-state frequencies of CMV-specific CD4+ memory T cells are maintained in CMV-exposed subjects, and these cells are thought to play a key role in the immunologic control of this permanent infection. However, the essential components of this response are poorly defined. Here, we report the use of a step-wise application of flow cytometric and molecular techniques to determine the number and size of the TCR Vβ-defined clonotypes within freshly obtained CMV-specific CD4+ memory T cell populations of four healthy, CMV-exposed human subjects. This analysis revealed a stable clonotypic hierarchy in which 1-3 dominant clonotypes are maintained in concert with more numerous subdominant and minor clonotypes. These dominant clonotypes accounted for 10-50% of the overall CMV response, and comprised from 0.3 to 4.0% of peripheral blood CD4+ T cells. Two subjects displayed immunodominant responses to single epitopes within the CMV matrix phosphoprotein pp65; these single epitope responses were mediated by a single dominant clonotype in one subject, and by multiple subdominant and minor clonotypes in the other. Thus, the CMV-specific CD4+ T cell memory repertoire in normal subjects is characterized by striking clonotypic dominance and the potential for epitope focusing, suggesting that primary responsibility for immunosurveillance against CMV reactivation rests with a handful of clones recognizing a limited array of CMV determinants. These data have important implications for the understanding of mechanisms by which a genetically stable chronic viral pathogen such as CMV is controlled, and offer possible insight into the failure of such control for a genetically flexible pathogen like HIV-1.

Original languageEnglish (US)
Pages (from-to)1151-1163
Number of pages13
JournalJournal of Immunology
Volume167
Issue number3
DOIs
StatePublished - Aug 1 2001

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Bitmansour, A. D., Waldrop, S. L., Pitcher, C. J., Khatamzas, E., Kern, F., Maino, V. C., & Picker, L. J. (2001). Clonotypic structure of the human CD4+ memory T cell response to cytomegalovirus. Journal of Immunology, 167(3), 1151-1163. https://doi.org/10.4049/jimmunol.167.3.1151