The T-cell receptor is not hardwired to engage MHC ligands

Proc Natl Acad Sci U S A. 2012 Nov 6;109(45):E3111-8. doi: 10.1073/pnas.1210882109. Epub 2012 Oct 17.

Abstract

The bias of αβ T cells for MHC ligands has been proposed to be intrinsic to the T-cell receptor (TCR). Equally, the CD4 and CD8 coreceptors contribute to ligand restriction by colocalizing Lck with the TCR when MHC ligands are engaged. To determine the importance of intrinsic ligand bias, the germ-line TCR complementarity determining regions were extensively diversified in vivo. We show that engagement with MHC ligands during thymocyte selection and peripheral T-cell activation imposes remarkably little constraint over TCR structure. Such versatility is more consistent with an opportunist, rather than a predetermined, mode of interface formation. This hypothesis was experimentally confirmed by expressing a hybrid TCR containing TCR-γ chain germ-line complementarity determining regions, which engaged efficiently with MHC ligands.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Lineage / immunology
  • Complementarity Determining Regions / genetics
  • Complementarity Determining Regions / immunology
  • Germ Cells / immunology
  • Ligands
  • Major Histocompatibility Complex / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Mutation / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / chemistry
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • Receptors, Antigen, T-Cell, gamma-delta / immunology
  • Recombination, Genetic / genetics
  • Selection, Genetic
  • Thymus Gland / immunology

Substances

  • Complementarity Determining Regions
  • Ligands
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta