Positive selection of self-MHC-reactive T cells by individual peptide-MHC class II complexes

被引:17
作者
Barton, GM
Beers, C
deRoos, P
Eastman, SR
Gomez, ME
Forbush, KA
Rudensky, AY
机构
[1] Univ Washington, Sch Med, Cellular & Mol Biol Program, Seattle, WA 98195 USA
[2] Univ Washington, Sch Med, Dept Immunol, Seattle, WA 98195 USA
[3] Univ Washington, Sch Med, Howard Hughes Med Inst, Seattle, WA 98195 USA
关键词
thymus; CD4 T cells; development; T cell specificity; mice;
D O I
10.1073/pnas.102645699
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
If T cells require specific interactions with MHC-bound peptides during positive selection, then the specificities of T cells selected by one peptide should be distinct from those selected by another. We have examined positive selection of CD4 T cells in four strains of mice, each overexpressing a different peptide-l-All(Ab) complex. We show that a subset of CD4 T cells is selected by the overexpressed peptide and that the specificities of the CD4 T cells, as measured by reactivity to wild-type antigen-presenting cells, vary greatly depending on which peptide is overexpressed. These differences in specificity are mediated through positive selection not negative selection. Each of the four peptide-A(b) complexes appears to adopt a different conformation, and these differences correlate with the differences in reactivity. Our results suggest that individual peptide-MHC complexes positively select different subsets of self-MHC-reactive T cells and that the conformation of the peptide-MHC complex may contribute to this process.
引用
收藏
页码:6937 / 6942
页数:6
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