T cell immunodominance and maintenance of memory regulated by unexpectedly cross-reactive pathogens

Michael A. Brehm, Amelia K. Pinto, Keith A. Daniels, Jonathan P. Schneck, Raymond M. Welsh, Liisa K. Selin

Research output: Contribution to journalArticlepeer-review

218 Scopus citations

Abstract

We show here that T cell cross-reactivity between heterologous viruses influences the immunodominance of virus-specific CD8+ T cells by two mechanisms. First, T cells specific for cross-reactive epitopes dominate acute responses to viral infections; second, within the memory pool, T cells specific for cross-reactive epitopes are maintained while those specific for non-cross-reactive epitopes are selectively lost. These findings suggest an immunological paradigm in which viral infections shape the available T cell repertoire, causing alterations in the hierarchies of both the primary and memory CD8+ T cell responses elicited by subsequent viral infections. Thus, immunodominance is a function of the host's previous exposure to unrelated pathogens, and this may have an impact on protective immunity and immunopathology.

Original languageEnglish
Pages (from-to)627-634
Number of pages8
JournalNature Immunology
Volume3
Issue number7
DOIs
StatePublished - 2002

Bibliographical note

Funding Information:
Acknowledgments We thank B. S. Sheridan for excellent technical assistance. Supported by National Institutes of Health research grants AR-35506,AI-17672 and AI-46629 (to R. M.W.),AI-46578 (to L. K. S.),AI-29575,AI-44129 and NMSS (RG 2637 A2/1) (to J. P. S.); training grant AI-07439 (to M.A. B.) and, in part, by a center grant DK-32520.

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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