A role for the region encompassing the c" strand of a TCR V alpha domain in T cell activation events

J Immunol. 2000 Jul 15;165(2):820-9. doi: 10.4049/jimmunol.165.2.820.

Abstract

The distinct strand topology of TCR V alpha domains results in a flatter surface in the region encompassing the c" strand than the corresponding region in Ig V domains. In the current study a possible role for this region in T cell activation has been investigated by inserting a potential glycosylation site at V alpha residue 82. This residue is in proximity to the c" strand and distal to the putative interaction site for cognate peptide:MHC ligand. An additional N-linked carbohydrate at this position would create a protrusion on the V alpha domain surface, and this may interfere with TCR aggregation and/or recruitment of signaling molecules. The modified TCR has been expressed in transfected T cells, and the phenotype following stimulation has been compared with that of cells expressing the wild-type TCR. The mutation has significant effects on activation-induced cell death and TCR internalization, but, unexpectedly, does not affect IL-2 secretion. Furthermore, analyses with tetrameric, peptide:MHC class II complexes suggest that the mutation decreases the ability of the TCR to aggregate into a configuration compatible with avid binding by these multivalent ligands.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal / analysis
  • Apoptosis / genetics
  • Apoptosis / immunology
  • Cell Line
  • Down-Regulation / genetics
  • Down-Regulation / immunology
  • Immunoblotting
  • Interleukin-2 / metabolism
  • Lymphocyte Activation* / genetics
  • Mice
  • Myelin Basic Protein / genetics
  • Myelin Basic Protein / immunology
  • Myelin Basic Protein / pharmacology
  • Peptide Fragments / genetics
  • Peptide Fragments / immunology
  • Peptide Fragments / pharmacology
  • Phosphotyrosine / immunology
  • Protein Structure, Tertiary
  • Receptors, Antigen, T-Cell, alpha-beta / antagonists & inhibitors
  • Receptors, Antigen, T-Cell, alpha-beta / chemistry
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / physiology*
  • Recombinant Proteins / immunology
  • Recombinant Proteins / pharmacology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*
  • Transfection / immunology

Substances

  • Antibodies, Monoclonal
  • Interleukin-2
  • Myelin Basic Protein
  • Peptide Fragments
  • Receptors, Antigen, T-Cell, alpha-beta
  • Recombinant Proteins
  • myelin basic protein 1-11
  • Phosphotyrosine