T-cell receptor is not hardwired to engage MHC ligands

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-l...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2012-11, Vol.109 (45), p.E3111-E3118
Main Authors: Holland, Stephen J, Bartok, Istvan, Attaf, Meriem, Genolet, Raphael, Luescher, Immanuel F, Kotsiou, Eleni, Richard, Ashkenaz, Wang, Edward, White, Matthew, Coe, David J, Chai, Jian-Guo, Ferreira, Cristina, Dyson, Julian
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Base Sequence
Bias
Biological Sciences
Cell Lineage - immunology
Complementarity Determining Regions - genetics
Complementarity Determining Regions - immunology
Germ Cells - immunology
hybrids
Ligands
Major Histocompatibility Complex - immunology
Mice
Mice, Inbred C57BL
Molecular Sequence Data
Mutation - genetics
PNAS Plus
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
Studies
T cell receptors
T-lymphocytes
thymocytes
Thymus Gland - immunology
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1210882109