TRANSMEMBRANE-4 SUPERFAMILY PROTEINS CD81 (TAPA-1), CD82, CD63, AND CD53 SPECIFICALLY ASSOCIATE WITH INTEGRIN ALPHA(4)BETA(1) (CD49D CD29)/

Anti-alpha(4) integrin mAb coprecipitated CD81 (TAPA-1), a 25-kDa cell surface protein, from various alpha(4) beta(1)-positive hemopoietic c ell lines, including Molt4, Jurkat, Ramos, and alpha(4)-transfected K5 62 (KX4C4) cells. In reciprocal experiments, the integrin alpha(4) bet a(1) (VLA4, CD49d/CD29) could be reprecipitated from CD81 immunoprecip itates. Anti-alpha(4) integrin mAb also coprecipitated CD81 from the a lpha(4) beta(7)-positive B cell line RPMI 8866. In contrast, no CD81 w as identified in alpha(2) beta(1), alpha(5) beta(1), or alpha(L) beta( 2) immunoprecipitates. Abs to other members of the transmembrane-4 sup erfamily, including CD53, CD63, and CD82, also coprecipitated alpha(4) beta(1). As shown by confocal microscopy, CD81 and CD82 colocalized w ith alpha(4) beta(1) in cell surface clusters. The cytoplasmic domain of the alpha(4) integrin was not necessary for alpha(4) beta(1)/CD81 a ssociation, nor was the association influenced by divalent cations, ED TA, integrin-activating mAb, or alpha(4) subunit cleavage. Notably, tw o independent alpha(4) adhesion-deficient mutants (D346E and D408E) we re deficient in their ability to associate with CD81. Thus, CD81 and o ther transmembrane-4 superfamily members may participate in functional ly relevant interactions with alpha(4) beta(1) and other integrins.