Altered positive selection due to corecognition of floppy peptide/MHC II conformers supports an integrative model of thymic selection.
Thymocytes bearing the E alpha 52-68/I-A(b) complex-specific 1H3.1 alpha beta T cell antigen receptor are positively selected in Ab-Ep [Ab-Ep transgenic, invariant chain (Ii)(-/-), I-A beta(b-/-)] mice, where I-A(b) molecules present only E alpha 52-68. Although Ii reintroduction led to deletion, I-A beta(b) reintroduction disrupted positive selection. T cell antigen receptor transgenic Ab-Ep I-A beta(b+) mice had a large thymus with an increased absolute number of CD4(+)CD8(+) cells and no overt signs of deletion. Unlike Ab-Ep Ii(+) antigen-presenting cells, Ab-Ep I-A beta(b+) antigen-presenting cells did not activate 1H3.1 T cells. However, their capacity to present E alpha 52-68 was intact. Thus, positive selection of 1H3.1 thymocytes on the tight compact E alpha 52-68/I-A(b) complex is neutralized by the corecognition of loose compact self-peptide/I-A(b) conformers that do not interfere with the cognate activation of mature 1H3.1 T cells. The data support the notion that the integration of distinct signals generated by the simultaneous recognition of multiple self-peptide/MHC complexes directs intrathymic selection of T cells.
Viret
Christophe
C
Howard Hughes Medical Institute and Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
He
Xin
X
Janeway
Charles A
CA
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001483:Base Sequence; D017931:DNA Primers; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013950:Thymus Gland / Q000276:immunology*
D017931:DNA Primers; D000949:Histocompatibility Antigens Class II