Permissive recognition during positive selection

Tomasz J. Pawlowski, Michael D. Singleton, Dennis Y. Loh, Rance Berg, Uwe D. Staerz

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


In the periphery αβ T lymphocytes recognize antigens in conjunction with major histocompatibility complex (MHC) molecules. In the thymus immature T cells are positively selected on MHC molecules in the apparent absence of cognate peptides. Thus, at different developmental stages a T cell responds to different epitopes, yet uses the identical αβ T cell antigen receptor (TcR). To explain this paradox it has been hypothesized that during positive selection immature T cells see peptides/ligands unique to the thymus, are selected by specific antagonists related to their cognate peptides, or are driven by lowered affinity thresholds of their TcR. Though different in detail, these theories rely on defined peptides uniquely matched to select certain TcR. However, we find that in a TcR-transgenic (TcR(trans)+) mouse severely limiting the diversity of peptides does not impair positive selection. We show that many unrelated peptides, including some naturally occurring on the cell surface, induce maturation of CD4-CD8+TcR(high) thymocytes. The same peptides when presented in conjunction with the selecting MHC molecule, are not recognized by peripheral T cells expressing the same TcR(trans). Therefore, these findings point to a promiscuous rather than discriminate recognition mode used by immature T cells.

Original languageEnglish
Pages (from-to)851-857
Number of pages7
JournalEuropean Journal of Immunology
Issue number4
StatePublished - Apr 1996


  • Peptide recognition
  • Positive selection
  • T lymphocyte


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