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

Annu Rev Immunol. 2010:28:275-94. doi: 10.1146/annurev-immunol-030409-101253.


Millions of T cells are produced in the thymus, each expressing a unique alpha/beta T cell receptor (TCR) capable of binding to a foreign peptide in the binding groove of a host major histocompatibility complex (MHC) molecule. T 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.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Ligands
  • Major Histocompatibility Complex / immunology*
  • Peptides / immunology*
  • Receptors, Antigen, T-Cell / immunology
  • T-Lymphocytes / immunology*
  • Thymus Gland / immunology


  • Ligands
  • Peptides
  • Receptors, Antigen, T-Cell