Murine T cells express a cell surface receptor for multiple extracellular matrix proteins. Identification and characterization with monoclonal antibodies.
Cell-cell and cell-extracellular (ECM) protein interactions are mediated through heterodimers termed integrins. We have demonstrated that dendritic epidermal T cell (DETC) lines adhere to the ECM proteins, fibronectin, fibrinogen, and vitronectin but not to collagen, laminin, or control proteins. This adhesion was blocked by the tetrapeptide RGDS, but not the control peptide, RGES. We have derived a hamster mAb H9.2B8, and a rat mAb, 8.18E12, from immunizations with DETC lines. The mAbs in combination, but not individually, specifically inhibited the adhesion of DETC lines to fibronectin, fibrinogen, and vitronectin. Immunoprecipitation analysis revealed that both mAbs reacted with a heterodimer composed of noncovalently linked 140- and 95-kD subunits. The 140-kD subunit can be reduced to 120- and 23-kD fragments. Although the two mAbs did not cross-compete for binding to DETC, sequential immunoprecipitation studies indicated that they react with the same 120-kD fragment. While all DETC cell lines and several T cell clones were reactive with the mAbs, the mAbs were not reactive with normal spleen, lymph node, thymus, or skin. Stimulation of splenic T cells with Con A or allogeneic cells induced mAb reactivity after 1 wk in vitro. These data demonstrate that a single lymphocyte receptor, with biochemical features characteristic of integrins, mediates RGD-dependent binding to the ECM proteins, fibronectin, fibrinogen, and vitronectin. Furthermore, since this integrin is expressed by long-term activated T cells, this receptor may play a physiological role in T cell function.
Maxfield
S R
SR
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
Moulder
K
K
Koning
F
F
Elbe
A
A
Stingl
G
G
Coligan
J E
JE
Shevach
E M
EM
Yokoyama
W M
WM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D000954:Antigens, Surface / Q000032:analysis* / Q000096:biosynthesis / Q000276:immunology; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D015815:Cell Adhesion Molecules; D002460:Cell Line; D006224:Cricetinae; D003713:Dendritic Cells / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006825:Hybridomas / Q000378:metabolism; D016023:Integrins; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000276:immunology; D051379:Mice; D008970:Molecular Weight; D011233:Precipitin Tests; D051381:Rats; D011917:Rats, Inbred Lew; D011971:Receptors, Immunologic / Q000032:analysis* / Q000096:biosynthesis / Q000276:immunology; D013601:T-Lymphocytes / Q000378:metabolism*; D014018:Tissue Distribution; D019096:Vitronectin
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D005353:Fibronectins; D006023:Glycoproteins; D016023:Integrins; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D019096:Vitronectin; D005340:Fibrinogen