Homotypic leukocyte aggregation triggered by a monoclonal antibody specific for a novel epitope expressed by the integrin beta 1 subunit: conversion of nonresponsive cells by transfecting human integrin alpha 4 subunit cDNA.
The monoclonal antibody 33B6 was found to be specific for the beta 1 integrin subunit. Treatment of leukocytes with this antibody induced a vigorous homotypic aggregation that had similar physiologic conditions as aggregation induced by a monoclonal antibody specific for the alpha 4 subunit. Expression of a beta 1 subunit on the cell surface was not sufficient for mAb 33B6-mediated aggregation to occur, since cells of the K562 erythroleukemia line failed to respond even though they expressed the beta 1 subunit and the 33B6 epitope. However, after transfection with cDNA encoding the alpha 4 subunit, K562 cells acquired the ability to aggregate in response to mAb 33B6 binding. By contrast, mAb 33B6 blocked cell binding to the endothelial surface protein vascular cell adhesion molecule-1 and the extracellular matrix protein fibronectin. These results suggest that the beta 1 epitope defined by mAb 33B6 may play a novel role in regulating leukocyte adhesive interactions.
Bednarczyk
J L
JL
Department of Immunology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Wygant
J N
JN
Szabo
M C
MC
Molinari-Storey
L
L
Renz
M
M
Fong
S
S
McIntyre
B W
BW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002449:Cell Aggregation; D002461:Cell Line, Transformed; D004247:DNA / Q000235:genetics; D000939:Epitopes / Q000276:immunology; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007153:Immunologic Deficiency Syndromes / Q000473:pathology; D039041:Integrin alpha4beta1; D016023:Integrins / Q000276:immunology* / Q000378:metabolism; D004915:Leukemia, Erythroblastic, Acute; D007962:Leukocytes / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured; D019010:Vascular Cell Adhesion Molecule-1
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D000939:Epitopes; D005353:Fibronectins; D007074:Immunoglobulin G; D039041:Integrin alpha4beta1; D016023:Integrins; D011993:Recombinant Fusion Proteins; D019010:Vascular Cell Adhesion Molecule-1; D004247:DNA