Affinity of thymic self-peptides for the TCR determines the selection of CD8+ T lymphocytes in the thymus

Bertram T. Ober, Qinghui Hu, Joseph T. Opferman, Sarah Hagevik, Nancy Chiu, Chyung Ru Wang, Philip G. Ashton-Rickardt*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Experiments with synthetic antigen peptides have suggested that a critical parameter that determines the developmental fate of an immature thymocyte is the affinity of interaction between TCR and self-peptide/MHC expressed on thymic stromal cells. To test the physiological relevance of this model for thymocyte development, we determined the affinity of the anti-HY TCR (B6.2.16) expressed on CD8+ cells for thymic self-peptide/H-2Db tetramers, then examined the ability of these self-peptides to determine the outcome of B6.2.16 CD8 cell selection in the thymus. The B6.2.16 TCR bound the male HY self-antigen with high affinity. Thymic self-peptides, which are highly abundant on the surface of thymic epithelial cells, bound the B6.2.16 TCR with low affinity. The ability of self-peptides to trigger positive or negative selection of B6.2.16 CD8 cells in cultured fetal thymi was determined by the relative affinity of self-peptide/H-2Db for the B6.2.16 TCR. High-affinity binding of the HY self-peptide resulted in B6.2.16 TCR complex ζ chain phosphorylation and the negative selection of B6.2.16 CD8 cells. Low-affinity binding of thymic self-peptides to B6.2.16 TCR resulted in the positive selection of B6.2.16 CD8 cells. Differences between the binding affinities of self-peptides to B6.2.16 TCR accounted for the self-peptide specificity of B6.2.16 CD8 cell positive selection. We conclude that the relative affinity of TCR for thymic self-peptide/class I MHC is a critical parameter in determining fate of CD8+ cells during thymic selection.

Original languageEnglish (US)
Pages (from-to)1353-1363
Number of pages11
JournalInternational Immunology
Volume12
Issue number9
DOIs
StatePublished - 2000

Keywords

  • MHC
  • T cell differentiation
  • Thymocyte development

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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