DISTINCT STRUCTURAL AND FUNCTIONAL EPITOPES OF THE ALPHA(E)BETA(7) INTEGRIN

Intestinal intraepithelial lymphocytes (iIEL) are predominantly CD3(+), CD8(+) T lymphocytes located above or adjacent to the mucosal basement membrane. Although they are positioned to interact with intercellular luminal antigen or with enterocytes, the function of iIEL remains unknown. Most (>85%) of the iIEL express the alpha(E) beta(7) integrin which appears to be involved in the adhesion of lymphocytes to epithelial cells. We report the characterization of three monoclonal antibodies (mAb) termed alpha E7-1, alpha E7-2, and alpha E7-3, that react with the alpha(E) beta(7) integrin recognized by the previously described mAb HML-1 as demonstrated by identical sodium dodecyl sulfate - polyacrylamide gel electrophoresis mobility and charge. Flow cytometric analysis of antibody cross-blocking indicated that these mAb recognize distinct epitopes of alpha(E) beta(7). While all of the mAb were capable of blocking the adhesion of cultured iIEL to a breast epithelial cell line, only HML-1 and alpha E7-1 (which recognize an identical or closely related epitope) were co-stimulatory with suboptimal concentrations of atni-CD3 mAb in inducing proliferation of cultured iIEL. Thus, these mAb appear to recognize functionally distinct epitopes of alpha(E) beta(7) and will be useful to study relationships between the structure and function of this integrin.