Glycosylation-dependent interaction of Jacalin with CD45 induces T lymphocyte activation and Th1/Th2 cytokine secretion.
Jacalin, an alpha-O-glycoside of the disaccharide Thomsen-Friedenreich antigen (galactose beta1-3 N-acetylgalactosamine, T-antigen)-specific lectin from jackfruit seeds, has been shown to induce mitogenic responses and to block infection by HIV-1 in CD4+ T lymphocytes. The molecular mechanism underlying Jacalin-induced T cell activation has not been elucidated completely yet. In the present study, protein tyrosine phosphatase (PTPase) CD45 was isolated from a Jurkat T cell membrane fraction as a major receptor for Jacalin through affinity chromatography and mass spectrometry. CD45, which is highly glycosylated and expressed exclusively on the surface of lymphocytes, is a key regulator of lymphocyte signaling, playing a pivotal role in activation and development. We found that the lectin induced significant IL-2 production by a CD45-positive Jurkat T cell line (JE6.1) and primary T cells. However, this effect did not occur in a CD45-negative Jurkat T cell line (J45.01) and was blocked completely by a specific CD45 PTPase inhibitor in Jurkat T (JE6.1) and primary T cells. Furthermore, we also observed that Jacalin caused a marked increase in IL-2 secretion in response to TCR ligation and CD28 costimulation and contributed to Th1/Th2 cytokine production by activating CD45. Jacalin increased CD45 tyrosine phosphatase activity, which resulted in activation of the ERK1/2 and p38 MAPK cascades. Based on these findings, we propose a new, immunoregulatory model for Jacalin, wherein glycosylation-dependent interactions of Jacalin with CD45 on T cells elevate TCR-mediated signaling, which thereby up-regulate T cell activation thresholds and Th1/Th2 cytokine secretion.
Baba
Makoto
M
Research Center for Glycobiotechnology, Ritsumeikan University, Shiga 525-8577, Japan.
Yong Ma
Bruce
B
Nonaka
Motohiro
M
Matsuishi
Yukari
Y
Hirano
Makoto
M
Nakamura
Natsuko
N
Kawasaki
Nana
N
Kawasaki
Nobuko
N
Kawasaki
Toshisuke
T
D002999:Clone Cells; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006031:Glycosylation; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D019169:Jurkat Cells; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D008213:Lymphocyte Activation; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D037121:Plant Lectins / Q000378:metabolism* / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D011975:Receptors, Mitogen / Q000302:isolation & purification* / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D007376:Interleukin-2; D037121:Plant Lectins; D011948:Receptors, Antigen, T-Cell; D011975:Receptors, Mitogen; C043696:jacalin; C519907:jacalin receptor, human; D020929:Mitogen-Activated Protein Kinase Kinases; D017493:Leukocyte Common Antigens