Int Immunol. 2000 Sep;12(9):1353-63. Unique Identifier : AIDSLINE MED/20425427
Ober BT; Hu Q; Opferman JT; Hagevik S; Chiu N; Wang CR; Ashton-Rickardt PG; Department of Pathology, University of Chicago, 924 E. 57th; Street, R414, IL 60637, USA.

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-2D(b) 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-2D(b) for the B6.2.16 TCR. High-affinity binding of the HY self-peptide resulted in B6.2.16 TCR complex zeta 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.

001230
A00C0938

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