CD4 and CD8 binding to MHC molecules primarily acts to enhance Lck delivery

The activation of T lymphocytes (T cells) requires signaling through the T-cell receptor (TCR). The role of the coreceptor molecules, CD4 and CD8, is not clear, although they are thought to augment TCR signaling by stabilizing interactions between the TCR and peptide—major histocompatibility (pMHC)...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2010-09, Vol.107 (39), p.16916-16921
Main Authors: Artyomov, Maxim N., Lis, Mieszko, Devadas, Srinivas, Davis, Mark M., Chakraborty, Arup K.
Format: Article
Language:English
Subjects:
Animals
Antigen-Presenting Cells - immunology
Antigens
Binding sites
Biochemistry
Biological Sciences
CD4 antigen
CD4 Antigens - chemistry
CD4 Antigens - metabolism
CD8 antigen
CD8 Antigens - chemistry
CD8 Antigens - metabolism
Cell activation
Cells
double prime T-cell receptor
Half lives
Humans
Kinases
Kinetics
Lck protein
Ligands
Lymphocyte Activation
Lymphocyte Specific Protein Tyrosine Kinase p56(lck) - metabolism
Lymphocytes
Lymphocytes T
Major Histocompatibility Complex
Molecules
Phosphorylation
Physical Sciences
Protein Transport
Receptors, Antigen, T-Cell - metabolism
Signal transduction
T cell antigen receptors
T lymphocytes
T-Lymphocytes - enzymology
T-Lymphocytes - immunology
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Summary:The activation of T lymphocytes (T cells) requires signaling through the T-cell receptor (TCR). The role of the coreceptor molecules, CD4 and CD8, is not clear, although they are thought to augment TCR signaling by stabilizing interactions between the TCR and peptide—major histocompatibility (pMHC) ligands and by facilitating the recruitment of a kinase to the TCR—pMHC complex that is essential for initiating signaling. Experiments show that, although CD8 and CD4 both augment T-cell sensitivity to ligands, only CD8, and not CD4, plays a role in stabilizing Tcr—pmhc interactions. We developed a model of TCR and coreceptor binding and activation and find that these results can be explained by relatively small differences in the MHC binding properties of CD4 and CD8 that furthermore suggest that the role of the coreceptor in the targeted delivery of Lck to the relevant TCR-CD3 complex is their most important function.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1010568107