Signaling from LFA-1 contributes signal transduction through CD2 alternative pathway in T cell activation.
LFA-1, a member of the integrin family of molecules, is involved in mediating cellular adhesion in all phases of the immune response, playing a role in the interaction of helper T cells as well as in killing of target cells by both cytotoxic T cells and natural killer cells. We have developed a monoclonal antibody, anti-HVS6B6, which recognizes a functionally unique epitope of the LFA-1 molecule. Although this mAb itself was not mitogenic against T cells, it induced a strong proliferative response when added to T cells with submitogenic concentrations of anti-CD2 (anti-T11(2) and anti-T11(3)) mAbs. In contrast, other anti-LFA-1 mAbs (CD11a and CD18) suppressed this anti-CD2 mAb-induced T cell proliferation. Kinetic studies showed that anti-HVS6B6 acts on an early event in CD2-mediated T cell activation. Although T11(3)-epitope expression induced by anti-T11(2) mAb was not affected by treatment of cells with anti-HVS6B6, both Ca2+ influx and phosphatidylinositol turnover induced by anti-CD2 mAbs were markedly enhanced by the pretreatment of T cells with anti-HVS6B6 mAb. These results indicate that the LFA-1 mediating signal contributes to a very early phase of signal transduction during CD2-mediated T cell activation.
Yamada
A
A
Department of Immunology, Kurume University School of Medicine, Japan.
Kaneyuki
T
T
Torimoto
Y
Y
Daley
J F
JF
Prado
C M
CM
Yokoyama
M M
MM
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D000956:Antigens, Viral / Q000032:analysis*; D018801:CD2 Antigens; D002118:Calcium / Q000378:metabolism; D000939:Epitopes / Q000032:analysis*; D015654:Herpesvirus 6, Human / Q000276:immunology*; D006801:Humans; D007962:Leukocytes / Q000276:immunology; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology* / Q000502:physiology; D010716:Phosphatidylinositols / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000945:Antigens, Differentiation, T-Lymphocyte; D000956:Antigens, Viral; D018801:CD2 Antigens; D000939:Epitopes; D016169:Lymphocyte Function-Associated Antigen-1; D010716:Phosphatidylinositols; D011971:Receptors, Immunologic; D002118:Calcium