T cell receptor antagonist peptides induce positive selection.
We have used organ culture of fetal thymic lobes from T cell receptor (TCR) transgenic beta 2M(-/-) mice to study the role of peptides in positive selection. The TCR used was from a CD8+ T cell specific for ovalbumin 257-264 in the context of Kb. Several peptides with the ability to induce positive selection were identified. These peptide-selected thymocytes have the same phenotype as mature CD8+ T cells and can respond to antigen. Those peptides with the ability to induce positive selection were all variants of the antigenic peptide and were identified as TCR antagonist peptides for this receptor. One peptide tested, E1, induced positive selection on the beta 2M(-/-) background but negative selection on the beta 2M(+/-) background. These results show that the process of positive selection is exquisitely peptide specific and sensitive to extremely low ligand density and support the notion that low efficacy ligands mediate positive selection.
Hogquist
K A
KA
Howard Hughes Medical Institute, Department of Immunology, University of Washington, Seattle 98195.
Jameson
S C
SC
Heath
W R
WR
Howard
J L
JL
Bevan
M J
MJ
Carbone
F R
FR
D000595:Amino Acid Sequence; D000818:Animals; D015704:CD4 Antigens / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D003433:Crosses, Genetic; D003602:Cytotoxicity, Immunologic; D005260:Female; D005333:Fetus; D005434:Flow Cytometry; D006183:H-2 Antigens / Q000276:immunology; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000276:immunology / Q000494:pharmacology; D009924:Organ Culture Techniques; D010047:Ovalbumin / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology* / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D013329:Structure-Activity Relationship; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*; D013950:Thymus Gland / Q000196:embryology / Q000276:immunology*; D001613:beta 2-Microglobulin / Q000172:deficiency
D015704:CD4 Antigens; D016827:CD8 Antigens; D006183:H-2 Antigens; D009842:Oligopeptides; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D001613:beta 2-Microglobulin; D010047:Ovalbumin