Identification of CD7 as a cognate of the human K12 (SECTM1) protein

CD7 is a 40-kDa protein found primarily on T, NK, and pre-B cells; the func tion of the CD7 protein in the immune system is largely unknown. The K12 (S ECTM1) protein was originally identified by its location just up-stream of the CD7 locus, The K12 gene encodes a transmembrane protein of unknown func tion. In order to clone a Kla-binding protein, we generated a soluble versi on of the human K12 protein by fusing its extracellular domain to the Fc po rtion of human IgG(1). Flow cytometry experiments showed that the K12-Fc fu sion protein bound at high levels to both human T and NK cells. Precipitati on experiments using K12-Fc on S-35-radiolabeled NK cells lysates indicated that the K12 cognate was an approximately 40-kDa protein. A human peripher al blood T cell cDNA expression library was screened with the K12-Fc protei n, and two independent, positive cDNA clones were identified and sequenced. Both cDNAs encoded the same protein, which was CD7, Thus, K12 and CD7 are cognate proteins that are located next to each other on human chromosome 17 q25. Additionally, we have cloned the gene encoding the mouse homologue of K12, shown that it maps near the mouse CD7 gene on chromosome 11, and estab lished that the mouse K12 protein binds to mouse, but not human, CD7. Mouse K12-Fc inhibited in a dose-dependent manner concanavalin A-induced prolife ration, but not anti-TcR alpha/beta induced proliferation, of mouse lymph n ode T cells, Human K12-Fc stimulated the up-regulation of CD25, CD54, and C D69 on human NK cells in vitro.