Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 109, Issue 45, Pages E3111-E3118Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1210882109
Keywords
MHC restriction; TCR
Categories
Funding
- Wellcome Trust
- UK Medical Research Council
- BBSRC [BB/F020732/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/F020732/1] Funding Source: researchfish
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The bias of alpha beta 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-gamma chain germ-line complementarity determining regions, which engaged efficiently with MHC ligands.
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