Specific disengagement of cell-bound anti-LAM-1 (anti-L-selectin) antibodies by aurintricarboxylic acid.
Brief treatment of human peripheral blood lymphocytes with the potential anti-HIV compound aurintricarboxylic acid (ATA) prompts the selective release of already bound L-selectin-specific anti-Leu8 and anti-LAM1-1 antibodies from the cells. Two other anti-LAM1 antibodies, anti-LAM1-3 and anti-LAM1-5 stay antigen-bound at the same time. Interestingly, the ATA-sensitive anti-Leu8 strongly competes with the ATA-resistant anti-LAM1-3 for binding. Photobleaching fluorescence resonance energy transfer (pFRET) measurements on flow-sorted cells suggests that these two antibodies compete for the same epitope, while anti-LAM1-5-FITC and anti-Leu8-PE bind to distinct sites, although they also compete for binding. Combining the data on competition, pFRET and ATA effect, we suggest that the ATA sensitive anti-Leu8 and resistant anti-LAM1-3 bind to overlapping but non-identical epitopes. This remarkably specific effect may be exploited for designing anti-inflammatory drugs that modulate leukocyte adhesion.
Szabó
G
G
Division of Research and Testing, F.D.A., Washington, DC 20204.
Weaver
J L
JL
Pine
P S
PS
Aszalos
A
A
D000937:Antigen-Antibody Reactions / Q000187:drug effects*; D001312:Aurintricarboxylic Acid / Q000494:pharmacology*; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D015815:Cell Adhesion Molecules / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D019041:L-Selectin; D008214:Lymphocytes / Q000187:drug effects*
D015815:Cell Adhesion Molecules; D019041:L-Selectin; D001312:Aurintricarboxylic Acid