A T cell receptor-specific blockade of positive selection

J Exp Med. 1999 Jan 4;189(1):13-24. doi: 10.1084/jem.189.1.13.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • Cytochrome c Group / immunology
  • Flow Cytometry
  • Histocompatibility Antigens Class II / immunology
  • Immunohistochemistry
  • Insect Proteins / immunology
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology
  • Major Histocompatibility Complex / immunology
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Peptide Fragments / immunology*
  • Receptors, Antigen, T-Cell / metabolism*
  • Spleen / cytology
  • Spleen / immunology
  • T-Lymphocytes / immunology*
  • Thymus Gland / cytology
  • Thymus Gland / immunology*

Substances

  • Antibodies, Monoclonal
  • Cytochrome c Group
  • Histocompatibility Antigens Class II
  • I-E-antigen
  • Insect Proteins
  • Peptide Fragments
  • Receptors, Antigen, T-Cell