title: CD4 and CD8 binding to MHC molecules primarily acts to enhance Lck delivery.
abstract: 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.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Maxim N
authors.initials: MN
authors.lastname: Artyomov
authors.forename: Mieszko
authors.initials: M
authors.lastname: Lis
authors.forename: Srinivas
authors.initials: S
authors.lastname: Devadas
authors.forename: Mark M
authors.initials: MM
authors.lastname: Davis
authors.forename: Arup K
authors.initials: AK
authors.lastname: Chakraborty
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015704:CD4 Antigens / Q000737:chemistry / Q000378:metabolism*; D016827:CD8 Antigens / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism*; D008285:Major Histocompatibility Complex; D021381:Protein Transport; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology*
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D011948:Receptors, Antigen, T-Cell; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)