Inhibition of cell proliferation with an HLA-A-specific monoclonal antibody.
A new mouse IgG2A monoclonal antibody--JD 12--is described, which was selected for its ability to inhibit peripheral blood mononuclear cell (PBMC) proliferation. Serologic, immunoprecipitation and immunoelectrophoretic studies showed JD12 to be monomorphically reactive with HLA-A molecules with an affinity of 10(9) M-1. JD12 was capable of inhibiting growth in resting or stimulated PBMC with an ID50 of 300 ng/ml in a time-dependent and dose-dependent manner without cytotoxicity. IgG, F(ab)2 and F(ab) were active. Growth stimulation by phorbol ester was not inhibited, suggesting that JD12 action occurred prior to protein kinase C activation. DNA and RNA synthesis were both slowed with a resulting G0/G1 block. Analysis of separated PBMC components showed that adherent cells displayed increased activity (clumping and RNA synthesis) upon JD12 binding. In addition, the inhibitory activity of JD12 could be transferred to new cultures by cell-free, IgG-free supernatant from JD12-treated PBMC, suggesting that the antiproliferative effects could be mediated, at least in part, in an indirect manner through an inhibitory factor. Therefore, potent, noncytotoxic inhibition of cell proliferation, DNA and RNA synthesis via MHC molecules can be mediated specifically through effects initiated by binding to HLA-A molecules alone.
Scheinberg
D A
DA
Memorial Sloan-Kettering Cancer Center, New York, NY.
Bull
M K
MK
Yang
S Y
SY
Class
K A
KA
Minniti
J G
JG
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D002453:Cell Cycle; D002455:Cell Division; D004247:DNA / Q000096:biosynthesis; D015234:HLA-A Antigens / Q000276:immunology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012313:RNA / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D015234:HLA-A Antigens; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D012313:RNA; D004247:DNA