Regulation of human intestinal intraepithelial lymphocyte cytolytic function by biliary glycoprotein (CD66a)

Human small intestinal intraepithelial lymphocytes (iIEL) are a unique popu lation of CD8 alpha beta(+) TCR-alpha beta(+) but CD28(-) T lymphocytes tha t may function in intestinal epithelial cell immunosurveillance. In an atte mpt to define novel cell surface molecules involved in iIEL function, we ra ised several mAbs against activated iIELs derived from the small intestine that recognized an Ag on activated, but not resting, iIELs, Using expressio n cloning and binding studies with Fc fusion proteins and transfectants, th e cognate Ag of these mAbs was identified as the N domain of biliary glycop rotein (CD66a), a carcinoembryonic Ag-related molecule that contains an imm une receptor tyrosine-based inhibitory motif. Functionally, these mAbs inhi bited the anti-CD3-directed and lymphokine-activated killer activity of the P815 cell line by iIELs derived from the human small intestine. These stud ies indicate that the expression of biliary glycoprotein on activated human iIELs and, potentially, other mucosal T lymphocytes is involved in the dow n-regulation of cytolytic function.