TY - JOUR
T1 - CD4 and CD8 binding to MHC molecules primarily acts to enhance Lck delivery
AU - Artyomov, Maxim N.
AU - Lis, Mieszko
AU - Devadas, Srinivas
AU - Davis, Mark M.
AU - Chakraborty, Arup K.
PY - 2010/9/28
Y1 - 2010/9/28
N2 - 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.
AB - 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.
KW - Computation
KW - Coreceptors
KW - Diffusion
KW - Stochastic process
KW - T-cell activation
UR - http://www.scopus.com/inward/record.url?scp=78049266750&partnerID=8YFLogxK
U2 - 10.1073/pnas.1010568107
DO - 10.1073/pnas.1010568107
M3 - Article
C2 - 20837541
AN - SCOPUS:78049266750
SN - 0027-8424
VL - 107
SP - 16916
EP - 16921
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 39
ER -