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Thymic selection reinterpreted

J I Elliot1

  • 1Section of Transplantation Biology, Clinical Research Centre, Harrow, Middx., U.K.

Immunological Reviews
|October 1, 1993
PubMed
Summary
This summary is machine-generated.

The T-cell receptor (TCR) repertoire in thymocytes naturally recognizes MHC/peptide complexes with high affinity. This suggests positive selection, not just tolerance, must dominate thymic T-cell development to prevent widespread T-cell deletion.

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Area of Science:

  • Immunology
  • T-cell biology
  • Thymic selection

Background:

  • The T-cell receptor (TCR) repertoire of unselected thymocytes exhibits a strong propensity for high-affinity recognition of MHC/peptide complexes.
  • This high-affinity recognition raises questions about the balance between negative selection (tolerance induction) and positive selection during T-cell development.

Purpose of the Study:

  • To present evidence that positive selection must be the dominant process in thymic T-cell development.
  • To propose a mechanism involving antagonistic peptides that could explain the dominance of positive selection.

Main Methods:

  • Theoretical presentation of evidence.
  • Hypothetical model of thymic selection processes.

Main Results:

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  • The unselected thymocyte TCR repertoire's high-affinity recognition implies that tolerance induction alone would lead to near-complete T-cell deletion or anergy.
  • Positive selection must therefore be capable of overriding or dominating negative selection.

Conclusions:

  • Positive selection is a critical and dominant process in thymic T-cell development.
  • Antagonistic peptides in the thymus may play a role in inhibiting deletion, thereby facilitating positive selection.