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Permissive recognition during positive selection

T J Pawlowski1, M D Singleton, D Y Loh

  • 1Department of Medicine, National Jewish Center of Immunology and Respiratory Medicine, Denver, CO 80206, USA.

European Journal of Immunology
|April 1, 1996
PubMed
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Immature T cells, or thymocytes, recognize a wide array of peptides during development, unlike mature T cells. This suggests T cell receptor recognition is promiscuous during thymic selection.

Area of Science:

  • Immunology
  • T cell biology
  • Molecular immunology

Background:

  • Alpha beta T lymphocytes recognize antigens with Major Histocompatibility Complex (MHC) molecules in the periphery.
  • Immature T cells undergo positive selection in the thymus on MHC molecules without cognate peptides, presenting a paradox for T cell receptor (TcR) specificity.

Purpose of the Study:

  • To investigate the peptide recognition mechanisms of immature T cells during thymic positive selection.
  • To reconcile the apparent paradox of identical TcRs recognizing different epitopes at distinct T cell developmental stages.

Main Methods:

  • Utilized a T cell receptor-transgenic (TcR(trans+)) mouse model.
  • Manipulated peptide diversity presented during thymic positive selection.
  • Assessed thymocyte maturation (CD4-CD8+TcR(high)) and peripheral T cell recognition.

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Main Results:

  • Severely limiting peptide diversity did not impair positive selection in the TcR(trans+) mouse.
  • Numerous unrelated peptides, including cell surface molecules, induced thymocyte maturation.
  • Peripheral T cells expressing the same TcR(trans) did not recognize these peptides when presented by MHC.

Conclusions:

  • Immature T cells exhibit promiscuous peptide recognition during thymic positive selection.
  • The recognition mode of immature T cells differs significantly from that of mature T cells.
  • Findings challenge existing theories relying on specific peptide-MHC interactions for T cell selection.