CD7 IS ASSOCIATED WITH CD3 AND CD45 ON HUMAN T-CELLS

The CD7 cluster of mAb identifies a 40-kDa glycopolypeptide that is pr esent on a major subset of human T cells. CD7 Ag mediates an accessory pathway of T cell activation in that cross-linked CD7 mAb are mitogen ic, and signals delivered via CD7 Ag stimulate integrin-mediated adhes ion. We have found that the CD7 molecule is associated with a tyrosine kinase whose major substrate is CD45. In vitro phosphorylation of CD7 , CD3, or CD45 immunoprecipitates prepared from lysates of human T cel ls showed a similar pattern of multiple phosphorylated polypeptides; i n addition, these immunoprecipitates phosphorylated a tyrosine kinase- specific peptide. Surface-iodinated T cells were lysed and immunopreci pitated with CD7, CD3, and CD45 mAb. Bands characteristic of CD45 and CD3 were identified in CD7 immunoprecipitates. Confirmation of an asso ciation of CD7 with CD3 and CD45 was obtained from Western blotting an d fluorescence resonance energy transfer experiments. Furthermore, we provide evidence using immunoprecipitation and Western blotting that C D7 exists as a homodimer. These data support the hypothesis that CD7 e xists in an oligomeric complex with CD3/TCR, the protein tyrosine phos phatase CD45, and a tyrosine kinase, thereby providing a physical basi s for the accessory role of the CD7 molecule in T cell activation.