Peyer's patch-specific lymphocyte homing receptors consist of a VLA-4-like alpha chain associated with either of two integrin beta chains, one of which is novel.
Integrins are heterodimeric cell surface proteins that mediate both cell-cell and cell-extracellular matrix interactions . We and others recently identified cDNAs encoding a novel integrin ß subunit, 07, in lymphocytes . We have now detected 07 mRNA in mouse TK-1 T lymphoma cells, which are known to express the putative Peyer's patch homing receptor a4ßP. We used an anti-peptide antiserum and a novel mAb against the 07 subunit to show that TK-1 cells express 07 as the only subunit associated with a4. We conclude that 07 and ßP are identical . We also show that activated peripheral blood T cells express a4ß7. We studied the function of a4ß7/a4ßP in TK-1 cells, which do not express very late antigen (VLA)-4 (a4ß1) . Cells adhered to intact fibronectin and to a fibronectin fragment containing the CS-1 region, but not to a THE ability to interact with a variety of cells or with proteins of the extracellular matrix is crucial for a variety of leukocyte functions, including cell activation, phagocytosis, recruitment to sites of inflammation, recirculation, and homing (for reviews see Stoolman, 1989 ; Butcher, 1990; Springer, 1990) . Many adhesion molecules expressed on T lymphocytes belong to the integrin family. Integrins are noncovalently linked heterodimers consisting of an a and a ß subunit that mediate cell-extracellular matrix as well as cell-cell interactions (Hynes, 1987; Ruoslahti, 1991) . The a and ß subunits each have a large extracellular domain, a short transmembrane region, and a cytoplasmic tail . At least 13 different a and eight different ß subunits have been identified to date ; these combine to produce at least 18 different integrin heterodimers . Both a and ß subunits participate in the determination ofligand specificity. The tripeptide RGD (Arg-Gly-Asp) is the recognition site for many of the integrins that bind to extracellular matrix proteins . Members of the 01 integrin subfamily (a1ß1 to a6ß1), also referred to as the very late antigens (VLA-1 to VLA-6), bind and mediate adhesion to several extracellular matrix proteins such as laminin, collagens, and fibronectin (Hemler, 1990) . © The Rockefeller University Press, 0021-9525/92/04/179/11 $2 .00 The Journal of Cell Biology, Volume 117, Number 1, April 1992 179-189 fragment containing the RGD sequence . Adhesion to fibronectin was inhibited by antibodies to a4, suggesting that a4ß7 is a fibronectin receptor. We confirmed that a4ß7 binds to the CS-1 region of fibronectin using affinity chromatography. TK-1 cell adhesion to the vascular cell adhesion molecule VCAM-1 was also inhibited by antibodies to a4, implying that a4ß7 also plays a role in the adherence of lymphocytes to endothelial cells . TK-1 cell binding to fibronectin and VCAM-1 is markedly increased by brief PMA stimulation . We also found that mAbs against a4 and 07 induce homotypic clustering of TK-1 cells . Taken together these results suggest that a4ß7/a4ßP recognizes some or all of the same widely distributed ligands recognized by VLA-4 (a4ß1) and that the role of a4ß7/ a4ßP may not be restricted to lymphocyte homing . a4ß1 (VLA-4) has been shown to be involved in at least three different kinds ofadhesive interactions . First, a4ß1 mediates cell adhesion to fibronectin by binding to the alternatively spliced C9-1 region of fibronectin (Wayner et al ., 1989 ; Mould et al ., 1990 ; Guan and Hynes, 1990) . Second, a4ß1 mediates T cell adhesion to endothelium by binding to the vascular cell adhesion molecule VCAM-1 (Elices et al ., 1990) . T cell activation causes rapid enhancement of c4ß1mediated binding to both fibronectin and VCAM-1 (Shimizu et al ., 1990a,ó) . Third, certain antibodies directed against the a4 subunit of a4ß1 induce homotypic lymphocyte clustering (Campanero et al ., 1990 ; Bednarczyk and McIntyre, 1990 ; Pulido et al ., 1991) . This clustering is dependent upon divalent cations . Clustering can be abolished by other antibodies directed against a4 and by some anti-01 antibodies, but not by antibodies against other integrins or VCAM-1 . It is possible that binding of anti-ce4 antibodies induces a conformational change in a4ß1 that allows a4ß1 to bind to an unidentified counterreceptor on adjacent cells. Alternatively, binding of anti-c«4 antibodies might cause clustering by triggering an a4ß1-mediated signal that activates other adhesion pathways .