Cell spreading distinguishes the mechanism of augmentation of T cell activation by integrin-associated protein/CD47 and CD28

Integrin-associated protein (IAP/CD47) is a 50 kDa transmembrane protein in itially defined as a regulator of pg integrin-mediated functions in neutrop hils, IAP also can synergize with the TCR in T cell activation independent of PQ integrins, To analyze the mechanism for IAP synergy with TCR, we expr essed in Jurkat cells a chimeric molecule, consisting of the Cole extracell ular domain, the CD7 transmembrane domain and the TCR zeta chain cytoplasmi c tail (CD16-7-zeta), which on its own is unable to induce IL-2 production. Ligation of IAP acted in synergy with TCR to induce IL-2 transcription and synthesis, but failed to synergize with the signal generated by CD16-7-zet a, while CD28 was a potent co-stimulator with both TCR and CD16-7-zeta, The failure of IAP to activate Jurkat together with CD16-7-zeta correlated wit h a lack of c-Jun N-terminal kinase, but not extracellular-signal-regulated kinase activation. Jurkat adhesion to anti-IAP, but not anti-CD28, induced cell spreading and the same domains of IAP required for augmentation of T cell activation were required to induce cell spreading, IAP synergy with TC R signaling likely results from its ability to stimulate adhesion to a liga nd-expressing surface or antigen-presenting cell (APC), rather than from in itiation of a novel signaling cascade. We conclude that a major role for li gation of IAP in T cell activation is to enhance the efficiency of TCR sign aling by causing T cells to spread on an APC or surface.