The human intraepithelial lymphocyte marker HML-1 is an integrin consisting of a beta 7 subunit associated with a distinctive alpha chain.

The membrane antigen defined by the monoclonal antibody (mAb) HML-1 is abundantly expressed on, and largely restricted to, the T cells which populate the intestinal epithelium. We show that the mature form of the antigen is a heterodimer comprising a 150-kDa alpha chain and a 120-kDa beta chain. Direct sequencing of tryptic peptides cleaved from the purified beta chain identified this polypeptide with the integrin beta 7 isotype. cDNA clones coding for the beta 7 chain have recently been isolated from T cell cDNA libraries, but the beta 7 chain had not been identified at the protein level. No information is available concerning the primary structure of the HML-1 alpha chain. We show that this subunit is synthesized as a precursor form that undergoes, like several other integrin alpha subunits, a post-translational cleavage of a peptide bond. Among the 11 human integrin alpha chains previously identified, 10 have biochemical features and/or a distribution different from those of HML-1 alpha. One, VLA alpha 4 (CD49d), has a molecular mass of 150 kDa and is expressed on HML-1+ cells but is not recognized by HML-1 mAb. We conclude that HML-1 is a novel member of the integrin family made of the beta 7 chain and of an as-yet-undescribed human alpha chain characterized by the post-translational cleavage of a 10-kDa peptide. HML-1 is, thus, probably the human counterpart of the mouse antigen M290.