LFA-1 decreases the antigen dose for T cell activation in vivo.
Leukocyte adhesion molecule leukocyte function-associated antigen (LFA)-1 not only mediates intercellular binding but also delivers co-stimulatory signals in T cells. LFA-1 has been shown to decrease the threshold of TCR signal and an antigen dose required for T cell activation and proliferation in vitro. However, physiological significance of the role of LFA-1 in TCR signal has remained unclear. We examined whether LFA-1 decreased the antigen dose for T cell activation in vivo. We showed here that, although collagen-induced arthritis (CIA) could not be induced by immunization and challenge with a standard amount of type-II collagen in LFA-1-deficient mice, a higher dose of the antigen did induce CIA in the absence of LFA-1. We also showed that CD4+ T cells could be primed by immunization with a high, but not low, dose of ovalbumin antigen in LFA-1-deficient mice. These results suggest that LFA-1 decreases the threshold of TCR signal for T cell activation in vivo as well as in vitro. Further studies using TCR-transgenic LFA-1-deficient mice showed that LFA-1 cooperated with TCR in sustained Erk1/2 phosphorylation. Moreover, TCR could induce sustained Erk1/2 phosphorylation in the absence of LFA-1 when T cells were stimulated with a high, but not low, dose of antigen, suggesting that LFA-1 may cooperate with TCR in sustaining Erk1/2 phosphorylation.
Wang
Yinan
Y
Department of Immunology, Institute of Basic Medical Sciences and Center for TARA, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Ten-nodai, Tsukuba, Ibaraki 305-8575, Japan.
Shibuya
Kazuko
K
Yamashita
Yumi
Y
Shirakawa
Jun
J
Shibata
Kai
K
Kai
Hirayasu
H
Yokosuka
Tadashi
T
Saito
Takashi
T
Honda
Shin-ichiro
S
Tahara-Hanaoka
Satoko
S
Shibuya
Akira
A
D000818:Animals; D030801:Animals, Genetically Modified; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology; D001169:Arthritis, Experimental / Q000209:etiology / Q000276:immunology*; D024043:Collagen Type II / Q000008:administration & dosage / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
D000941:Antigens; D024043:Collagen Type II; D016169:Lymphocyte Function-Associated Antigen-1; D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin