International Immunology, Vol. 12, No. 9, 1353-1363,
September 2000
© 2000 Japanese Society for Immunology
Affinity of thymic self-peptides for the TCR determines the selection of CD8+ T lymphocytes in the thymus
Gwen Knapp Center for Lupus and Immunology Research,
1 Department of Pathology,
2 Ben May Institute for Cancer Research and
3 Committee on Immunology, University of Chicago, 924 E. 57th Street, R414, IL 60637, USA
Correspondence to: P. G. Ashton-Rickardt
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 
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.
Keywords: MHC, T cell differentiation, thymocyte development
Transmitting editor: A. Singer
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