Convergence between CD98 and integrin‐mediated T‐lymphocyte co‐stimulation

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Abstract
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 β1 integrin antibody 18D3. Previously we have reported that co‐stimulatory activity of antibodies to integrins α4β1, α5β1, αLβ2 and α4β7 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 β1 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.