Monoclonal antibody-defined functional epitopes on the adhesion-promoting glycoprotein complex (CDw18) of human neutrophils.
We have evaluated the functional and immunochemical activities of three monoclonal antibodies (MoAbs) minimally reactive with adherence-defective neutrophils (PMN) from a patient with recurrent bacterial infections. In studies with normal PMN, MoAbs OKM1 and 60.1 both precipitate the same 165kd alpha-subunit (alpha M) within an alpha-beta heterodimer complex (CD11). The CD11 complex is part of a larger complex composed of four glycoproteins (CDw18) precipitated by MoAb 60.3, with properties suggesting that the CDw18 complex is equivalent to the Mac-1, LFA-1, p150, 95 glycoprotein family implicated in adherence-dependent leukocyte functions. PMN adherence to endothelium, spreading on surfaces, aggregation, and phagocytosis of zymosan particles were all inhibited in a dose-dependent fashion by MoAb 60.1 (analogous to previous studies with MoAb 60.3) while MoAb OKM1 had no effect. These findings unify previously disparate observations and suggest that a functionally active site on the adherence promoting glycoprotein complexes CD11 and CDw18 is distant from the alpha M epitope recognized by MoAb OKM1 but closely associated with the alpha M epitope recognized by MoAb 60.1 and the beta-epitope (or epitope created by alpha-beta quaternary structure) recognized by MoAb 60.3.
Wallis
W J
WJ
Hickstein
D D
DD
Schwartz
B R
BR
June
C H
CH
Ochs
H D
HD
Beatty
P G
PG
Klebanoff
S J
SJ
Harlan
J M
JM
D000911:Antibodies, Monoclonal / Q000502:physiology; D000937:Antigen-Antibody Reactions; D001798:Blood Proteins / Q000276:immunology* / Q000302:isolation & purification; D002448:Cell Adhesion; D002449:Cell Aggregation; D002465:Cell Movement; D004591:Electrophoresis, Polyacrylamide Gel; D004727:Endothelium / Q000502:physiology; D000939:Epitopes / Q000032:analysis / Q000276:immunology* / Q000302:isolation & purification; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006023:Glycoproteins / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D016177:Macrophage-1 Antigen; D009504:Neutrophils / Q000276:immunology* / Q000502:physiology; D010587:Phagocytosis; D011233:Precipitin Tests
D000911:Antibodies, Monoclonal; D001798:Blood Proteins; D000939:Epitopes; D006023:Glycoproteins; D016177:Macrophage-1 Antigen