Distinctive signaling pathways through CD82 and beta1 integrins in human T cells

• Published in: European journal of immunology Vol. 32; no. 5; pp. 1328 - 1337
• Main Authors: Iwata, Satoshi, Kobayashi, Hiroshi, Miyake-Nishijima, Rikako, Sasaki, Takahiro, Souta-Kuribara, Akiko, Nori, Mamoru, Hosono, Osamu, Kawasaki, Hiroshi, Tanaka, Hirotoshi, Morimoto, Chikao
• Format: Journal Article
• Language: English
• Published: Germany 01.05.2002
• Subjects: Adaptor Proteins, Signal Transducing; Antibodies, Monoclonal; Antigens, CD; Cell Line; DNA-Binding Proteins - metabolism; Humans; In Vitro Techniques; Integrin alpha4beta1; Integrin beta1 - metabolism; Integrins - metabolism; Interleukin-2 - genetics; Jurkat Cells; Kangai-1 Protein; Lymphocyte Activation; Membrane Glycoproteins - metabolism; NF-kappa B - metabolism; NFATC Transcription Factors; Nuclear Proteins; Phosphoproteins - metabolism; Phosphorylation; Proto-Oncogene Proteins; Receptors, Fibronectin - metabolism; Receptors, Lymphocyte Homing - metabolism; Signal Transduction - immunology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Transcription Factor AP-1 - metabolism; Transcription Factors - metabolism; Transcription, Genetic; Tyrosine - metabolism
• ISSN: 0014-2980

CD82, a member of tetraspan family (tetraspanin), is a multifunctional molecule that is involved in cell activation, costimulation, and cell spreading of T cells. Here we show that immobilized anti-CD82 monoclonal antibody (mAb) as well as anti-alpha4beta1 integrin mAb induced tyrosine phosphorylation of pp105/Crk-associated substrate lymphocyte type (Cas-L) in human peripheral T cells and H9 cells. Furthermore, one of anti-CD82 mAb (8E4), which induces homotypic aggregation of T cells and H9 cells but has no costimulatory activity, partially inhibited very late antigen (VLA)-4 integrin ligand-mediated costimulation of T cells, whereas it failed to inhibit VLA-5 integrin ligand-mediated costimulation. To further elucidate the relationship between CD82- and VLA-4-mediated signaling pathways we defined the IL-2 production by the costimulation of Jurkat T cells with marginal amount of Cas-L, and subsequently found that mAb against CD82 had strong costimulatory activity to CD3/TCR, whereas mAb against beta1 failed to do so in those cells. We have further demonstrated that this discrepancy between beta1 integrin- and CD82-mediated costimulation partly lies in differential activation of NF-AT, AP-1, and NF-kappaB in Jurkat T cells. In this study, although some functional overlap exists, we provide evidence for distinctive signaling of CD82- and beta1 integrin-mediated costimulation at the transcriptional level of IL-2 gene.