Ly6C induces clustering of LFA-1 (CD11a/CD18) and is involved in subtype-specific adhesion of CD8 T cells.
Ly6C is a hemopoietic cell differentiation Ag found on a subset of CD8 T cells in the periphery. It is involved in target cell killing by CTLs, augments TCR-mediated activation of IL-2 and IFN-gamma production in CD8 T cells, and regulates CD8 T cell homing in vivo. In this study, we show that cross-linking of Ly6C causes clustering of LFA-1 (CD11a/CD18) on the surface of CD8 T cells via a mechanism dependent on reorganization of actin cytoskeleton and intracellular protease, calpain, but not the phosphatidylinositol 3-kinase pathway. In the capillary flow-adhesion assay, Ly6C cross-linking significantly augments lymphocyte adhesion to endothelium, and this is inhibited by an Ab that blocks LFA-1 function. Furthermore, upon in vitro cross-linking and during in vivo homing into lymph nodes, Ly6C is transiently lost from cell surface but becomes re-expressed on lymph node-resident CD8 T cells. The abilities of Ly6C to induce LFA-1 clustering and to be re-expressed after signaling-associated down-regulation may be important in regulating the homing of CD8 T cells into lymph nodes and in subsequent steps of CD8 T cell activation and effector function that again involve LFA-1.
Jaakkola
Ilkka
I
MediCity Research Laboratory, University of Turku, Turku, Finland.
Merinen
Marika
M
Jalkanen
Sirpa
S
Hänninen
Arno
A
D000818:Animals; D000950:Antigens, Ly / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D040881:CD11a Antigen / Q000378:metabolism*; D018821:CD18 Antigens / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D002448:Cell Adhesion / Q000276:immunology; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D003432:Cross-Linking Reagents / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology / Q000502:physiology; D018984:Epitopes, T-Lymphocyte / Q000502:physiology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000502:physiology*
D000950:Antigens, Ly; D040881:CD11a Antigen; D018821:CD18 Antigens; D003432:Cross-Linking Reagents; D018984:Epitopes, T-Lymphocyte; D016169:Lymphocyte Function-Associated Antigen-1