On the composition of the preimmune repertoire of T cells specific for peptide-major histocompatibility complex ligands

Marc K. Jenkins, H. Hamlet Chu, James B. McLachlan, James J. Moon

Research output: Contribution to journalReview articlepeer-review

133 Scopus citations

Abstract

Millions of T cells are produced in the thymus, each expressing a unique α/β T cell receptor (TCR) capable of binding to a foreign peptide in the binding groove of a host major histocompatibility complex (MHC) molecule. TÂ cell-mediated immunity to infection is due to the proliferation and differentiation of rare clones in the preimmune repertoire that by chance express TCRs specific for peptide-MHC (pMHC) ligands derived from the microorganism. Here we review recent findings that have altered our understanding of how the preimmune repertoire is established. Recent structural studies indicate that a germline-encoded tendency of TCRs to bind MHC molecules contributes to the MHC bias of T cell repertoires. It has also become clear that the preimmune repertoire contains functionally heterogeneous subsets including recent thymic emigrants, mature naive phenotype cells, memory phenotype cells, and natural regulatory T cells. In addition, sensitive new detection methods have revealed that the repertoire of naive phenotype T cells consists of distinct pMHC-specific populations that consistently vary in size in different individuals. The implications of these new findings for the clonal selection theory, self-tolerance, and immunodominance are discussed.

Original languageEnglish (US)
Pages (from-to)275-294
Number of pages20
JournalAnnual Review of Immunology
Volume28
DOIs
StatePublished - Apr 23 2010

Keywords

  • Memory T cell
  • Naive T cell
  • Positive selection
  • Regulatory T cell

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