Modulation of T cell development by an endogenous altered peptide ligand.
T cells potentially encounter numerous endogenous peptides during selection in the thymus and in the periphery. We examined the impact of an endogenous peptide on in vivo T cell development, using a TCR transgenic mouse model based on a hemoglobin-specific T cell clone. In these mice, the transgenic beta chains paired with endogenous alpha chains. This led to a serendipitous primary reactivity to Ser69 peptide, an altered peptide ligand of the Hbd (64-76) epitope of the parent clone. Two Ser69-reactive T cell populations were identified. A smaller population of the Ser69-reactive T cells responded both to Ser69 and Hbd (64-76). A majority reacted only to Ser69, and not to Hbd(64-76); in fact, Hbd(64-76) was a specific TCR antagonist for these Ser69-only-reactive T cells. Thus, in this unique experimental system, Ser69 became an agonist, and Hbd (64-76) was an antagonist. Endogenous presentation of the antagonist ligand in the thymus selectively eliminated the high-avidity cells, while sparing low-avidity cells in the Ser69-reactive T cell repertoire. These results highlight how specificity guides developing T cells through a network of ligands and indicate that the endogenous peptide pool has a profound effect on T cell development and repertoire.
Hsu
B L
BL
Center for Immunology, Washington University School of Medicine, St. Louis, Missouri 63110.
Evavold
B D
BD
Allen
P M
PM
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002999:Clone Cells; D006454:Hemoglobins / Q000737:chemistry / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D008024:Ligands; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology
D006454:Hemoglobins; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D008024:Ligands; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; C079201:hemoglobin (64-76)