title: A T cell receptor-specific blockade of positive selection.
abstract: To investigate the influence of endogenous peptides on the developmental processes that occur during thymocyte selection, we have used monoclonal antibodies that preferentially recognize the major histocompatibility complex (MHC) molecule I-Ek when it is bound to the moth cytochrome c peptide (88-103). One of these antibodies (G35) specifically blocks the positive selection of transgenic thymocytes expressing a T cell receptor that is reactive to this peptide- MHC complex. Furthermore, G35 does not block the differentiation of transgenic T cells bearing receptors for a different I-Ek-peptide complex. This antibody recognizes a subset of endogenous I-Ek-peptide complexes found on a significant fraction of thymic antigen-presenting cells, including cortical and medullary epithelial cells. The sensitivity of G35 to minor alterations in peptide sequence suggests that the thymic peptide-MHC complexes that mediate the positive selection of a particular class II MHC-restricted thymocyte are structurally related to the complexes that can activate it in the periphery.
authors.affiliation: Howard Hughes Medical Institute, and the Department of Microbiology and Immunology, Stanford University, Stanford, California 94305, USA.
authors.forename: K K
authors.initials: KK
authors.lastname: Baldwin
authors.forename: P A
authors.initials: PA
authors.lastname: Reay
authors.forename: L
authors.initials: L
authors.lastname: Wu
authors.forename: A
authors.initials: A
authors.lastname: Farr
authors.forename: M M
authors.initials: MM
authors.lastname: Davis
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D003574:Cytochrome c Group / Q000276:immunology; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007150:Immunohistochemistry; D019476:Insect Proteins / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D003574:Cytochrome c Group; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D019476:Insect Proteins; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell