P126 (CDW101), A COSTIMULATORY MOLECULE PREFERENTIALLY EXPRESSED ON MUCOSAL T-LYMPHOCYTES

Intestinal mucosal lymphocytes are defined by their anatomic location within the epithelium (intraepithelial lymphocytes), the interstitium between the epithelial basement membrane and the underlying muscularis mucosa (lamina propria lymphocytes), or in organized lymphoid tissues (Peyer's patches), Although intestinal intraepithelial lymphocytes ha ve a distinct localization, their function has not been determined. To define cell surface proteins that are involved in intestinal intraepi thelial lymphocyte localization or function, cultured human mucosal ly mphocytes were used as immunogens to develop mAbs that react predomina ntly with this cell population in an immunohistochemical screening ass ay, Three mAbs were selected that subsequently were found by biochemic al analysis to identify a 200-kDa homodimeric polypeptide on 88 to 98% of CD3(+) mucosal lymphocytes but only 18 +/- 13% of PBLs, Expression on granulocytes and monocytes was also observed, This polypeptide has been termed p126 based on its SDS-PAGE-determined M(r) under reducing conditions, Cleveland digest maps demonstrated similarity between the p126 and CDw101 polypeptides, Determined amino acid sequence analysis of the purified p126 polypeptide revealed that it is the protein prod uct of the recently identified V7 gene, which has structural similarit ies to members of the Ig gene superfamily, Two of the anti-p126 mAbs w ere costimulatory with suboptimal concentrations of anti-CD3 mAb induc ing proliferation of cultured intestinal intraepithelial lymphocytes, Thus, we conclude that p126 is CDw101 encoded by a gene that predicts a seven-Ig domain chain-like structure, It has restricted expression p redominantly on mucosal T lymphocytes and appears to have a costimulat ory function of special relevance for CD28(-) T cells and for mucosal lymphocytes.