title: In vivo antagonism of a T cell response by an endogenously expressed ligand.
abstract: 3.L2 T cell receptor transgenic T cells are activated by the 64-76 peptide of the mouse hemoglobin d beta chain [Hb(64-76)], and their response is antagonized by the position 72 alanine substitution of this peptide (A72). To test the effect of this altered peptide ligand (APL) on 3.L2 T cell function in vivo, a transgene expressing A72 in major histocompatibility complex II positive cells (A72tg) has been introduced into mice. We demonstrate that 3.L2 T cells, when transferred to A72tg+ mice show a dramatically reduced proliferative response to Hb(64-76). Identical decreased responses were observed using T cells that developed in either A72tg+ or A72tg- hosts. This affect was not attributable to diminished precursor frequency, anergy, or competition for binding to I-Ek molecules. These results unequivocally demonstrate in vivo antagonism by an endogenous APL and characterize a class of self-peptides that, although inefficient in causing deletion in the thymus, effectively modulate T cell responses in the periphery.
authors.affiliation: Department of Pathology, Center for Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
authors.forename: D
authors.initials: D
authors.lastname: Basu
authors.forename: C B
authors.initials: CB
authors.lastname: Williams
authors.forename: P M
authors.initials: PM
authors.lastname: Allen
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D003433:Crosses, Genetic; D005434:Flow Cytometry; D006455:Hemoglobins, Abnormal / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D006455:Hemoglobins, Abnormal; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; C032001:hemoglobin D