Competitive displacement of pT alpha by TCR-alpha during TCR assembly prevents surface coexpression of pre-TCR and alpha beta TCR

J Immunol. 2000 Nov 15;165(10):5566-72. doi: 10.4049/jimmunol.165.10.5566.

Abstract

During alphabeta T cell development, CD4(-)CD8(-) thymocytes first express pre-TCR (pTalpha/TCR-beta) before their differentiation to the CD4(+)CD8(+) stage. Positive selection of self-tolerant T cells is then determined by the alphabeta TCR expressed on CD4(+)CD8(+) thymocytes. Conceivably, an overlap in surface expression of these two receptors would interfere with the delicate balance of thymic selection. Therefore, a mechanism ensuring the sequential expression of pre-TCR and TCR must function during thymocyte development. In support of this notion, we demonstrate that expression of TCR-alpha by immature thymocytes terminates the surface expression of pre-TCR. Our results reveal that expression of TCR-alpha precludes the formation of pTalpha/TCR-beta dimers within the endoplasmic reticulum, leading to the displacement of pre-TCR from the cell surface. These findings illustrate a novel posttranslational mechanism for the regulation of pre-TCR expression, which may ensure that alphabeta TCR expression on thymocytes undergoing selection is not compromised by the expression of pre-TCR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding, Competitive / immunology
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cell Membrane / immunology
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Dimerization
  • Disulfides / metabolism
  • Gene Expression Regulation / immunology
  • Genes, T-Cell Receptor alpha / physiology
  • Membrane Glycoproteins / antagonists & inhibitors
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, SCID
  • Mice, Transgenic
  • Protein Precursors / antagonists & inhibitors*
  • Protein Precursors / biosynthesis*
  • Protein Precursors / metabolism
  • Protein Processing, Post-Translational / immunology
  • RNA, Messenger / biosynthesis
  • Receptors, Antigen, T-Cell, alpha-beta / antagonists & inhibitors*
  • Receptors, Antigen, T-Cell, alpha-beta / biosynthesis*
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism
  • Receptors, Antigen, T-Cell, alpha-beta / physiology
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / metabolism*
  • Tumor Cells, Cultured

Substances

  • Disulfides
  • Membrane Glycoproteins
  • Protein Precursors
  • RNA, Messenger
  • Receptors, Antigen, T-Cell, alpha-beta
  • pre-T cell receptor alpha