Convergence between CD98 and integrin-mediated T-lymphocyte co-stimulation.
CD98 is a widely expressed cell surface heterodimeric glycoprotein, which is rapidly up-regulated upon activation of T lymphocytes. Monoclonal antibody (mAb) 80A10 recognizes an epitope on CD98 and in combination with CD3 antibody causes proliferation of peripheral blood T lymphocytes. CD98 co-stimulatory activity, mediated by either mAb 80A10 or 4F2, a well-characterized CD98-specific mAb, is blocked in the presence of the soluble beta1 integrin antibody 18D3. Previously we have reported that co-stimulatory activity of antibodies to integrins alpha4beta1, alpha5beta1, alphaLbeta2 and alpha4beta7 is inhibited by 18D3, whereas co-stimulation mediated by non-integrins was unaffected. Thus the non-integrin CD98 is uniquely sensitive to the inhibitory effects of beta1 integrin-blocking antibodies, which may reflect convergent signalling mechanisms between integrins and CD98. This is consistent with recent reports suggesting that CD98 may regulate integrin-mediated adhesive events.
Warren
A P
AP
Department of Biochemistry, St George's Hospital Medical School, London, UK.
Patel
K
K
Miyamoto
Y
Y
Wygant
J N
JN
Woodside
D G
DG
McIntyre
B W
BW
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000302:isolation & purification; D015703:Antigens, CD / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology*; D002460:Cell Line; D005434:Flow Cytometry; D027261:Fusion Regulatory Protein-1; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000276:immunology*; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008213:Lymphocyte Activation; D011233:Precipitin Tests; D011485:Protein Binding / Q000187:drug effects; D016201:Receptors, Lymphocyte Homing / Q000276:immunology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D017252:CD3 Complex; D002352:Carrier Proteins; D027261:Fusion Regulatory Protein-1; D039041:Integrin alpha4beta1; D016023:Integrins; D007476:Ionophores; D016201:Receptors, Lymphocyte Homing; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate