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

Int Immunol. 2000 Sep;12(9):1353-63. doi: 10.1093/intimm/12.9.1353.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 2
  • ATP-Binding Cassette Transporters / genetics
  • Animals
  • Autoantigens / immunology*
  • Autoantigens / isolation & purification
  • CD8-Positive T-Lymphocytes / immunology*
  • Epithelial Cells / immunology
  • Female
  • Fetus
  • H-2 Antigens
  • H-Y Antigen
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Peptide Fragments / immunology*
  • Peptide Fragments / isolation & purification
  • Receptors, Antigen, T-Cell / immunology*
  • Thymus Gland / cytology
  • Thymus Gland / immunology*

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 2
  • ATP-Binding Cassette Transporters
  • Autoantigens
  • H-2 Antigens
  • H-Y Antigen
  • Peptide Fragments
  • Receptors, Antigen, T-Cell
  • TAP1 protein, human
  • Tap1 protein, mouse