Positive selection of self-MHC-reactive T cells by individual peptide-MHC class II complexes.
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-1-A(b)(A(b)) 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.
Barton
Gregory M
GM
Molecular and Cellular Biology Program, Department of Immunology, University of Washington School of Medicine, Seattle, WA 98195, USA.
Beers
Courtney
C
deRoos
Paul
P
Eastman
Susan R
SR
Gomez
Marcela E
ME
Forbush
Katherine A
KA
Rudensky
Alexander Y
AY
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015815:Cell Adhesion Molecules; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D037102:Lectins; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D051918:Sialic Acid Binding Ig-like Lectin 2; D020696:rab5 GTP-Binding Proteins / Q000276:immunology
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D001324:Autoantigens; C497867:CD22 protein, human; C497868:Cd22 protein, mouse; D015815:Cell Adhesion Molecules; D000949:Histocompatibility Antigens Class II; D037102:Lectins; D010455:Peptides; D051918:Sialic Acid Binding Ig-like Lectin 2; C045084:invariant chain; D020696:rab5 GTP-Binding Proteins