TY - JOUR
T1 - Decreased binding of peptides-MHC class I (pMHC) multimeric complexes to CD8 affects their binding avidity for the TCR but does not significantly impact on pMHC/TCR dissociation rate
AU - Dutoit, Valérie
AU - Guillaume, Philippe
AU - Ayyoub, Maha
AU - Hesdorffer, Charles S.
AU - Luescher, Immanuel F.
AU - Valmori, Danila
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2003/5/15
Y1 - 2003/5/15
N2 - The CD8 coreceptor plays a crucial role in both T cell development in the thymus and in the activation of mature T cells in response to Ag-specific stimulation. In this study we used soluble peptides-MHC class I (pMHC) multimeric complexes bearing mutations in the CD8 binding site that impair their binding to the MHC, together with altered peptide ligands, to assess the impact of CD8 on pMHC binding to the TCR. Our data support a model in which CD8 promotes the binding of TCR to pMHC. However, once the pMHC/TCR complex is formed, the TCR dominates the pMHC/TCR dissociation rates. As a consequence of these molecular interactions, under physiologic conditions CD8 plays a key role in complex formation, resulting in the enhancement of CD8 T cell functions whose specificity, however, is determined by the TCR.
AB - The CD8 coreceptor plays a crucial role in both T cell development in the thymus and in the activation of mature T cells in response to Ag-specific stimulation. In this study we used soluble peptides-MHC class I (pMHC) multimeric complexes bearing mutations in the CD8 binding site that impair their binding to the MHC, together with altered peptide ligands, to assess the impact of CD8 on pMHC binding to the TCR. Our data support a model in which CD8 promotes the binding of TCR to pMHC. However, once the pMHC/TCR complex is formed, the TCR dominates the pMHC/TCR dissociation rates. As a consequence of these molecular interactions, under physiologic conditions CD8 plays a key role in complex formation, resulting in the enhancement of CD8 T cell functions whose specificity, however, is determined by the TCR.
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U2 - 10.4049/jimmunol.170.10.5110
DO - 10.4049/jimmunol.170.10.5110
M3 - Article
C2 - 12734357
AN - SCOPUS:0037884764
SN - 0022-1767
VL - 170
SP - 5110
EP - 5117
JO - Journal of Immunology
JF - Journal of Immunology
IS - 10
ER -