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 baseme nt membrane. Although they are positioned to interact with intercellul ar luminal antigen or with enterocytes, the function of iIEL remains u nknown. Most (>85%) of the iIEL express the alpha(E) beta(7) integrin which appears to be involved in the adhesion of lymphocytes to epithel ial cells. We report the characterization of three monoclonal antibodi es (mAb) termed alpha E7-1, alpha E7-2, and alpha E7-3, that react wit h the alpha(E) beta(7) integrin recognized by the previously described mAb HML-1 as demonstrated by identical sodium dodecyl sulfate - polya crylamide gel electrophoresis mobility and charge. Flow cytometric ana lysis of antibody cross-blocking indicated that these mAb recognize di stinct 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 clos ely related epitope) were co-stimulatory with suboptimal concentration s of atni-CD3 mAb in inducing proliferation of cultured iIEL. Thus, th ese mAb appear to recognize functionally distinct epitopes of alpha(E) beta(7) and will be useful to study relationships between the structu re and function of this integrin.