Naturally occurring catalytic antibodies: evidence for preferred development of the catalytic function in IgA class antibodies.
IgG class antibodies express catalytic activities rarely and at very low levels. Here, we studied polyclonal IgA and IgG preparations from healthy human sera and saliva for the ability to hydrolyze model peptidyl-aminomethylcoumarin (peptide-AMC) substrates. These substrates permit objective evaluation of the catalytic potential of the antibody classes with minimal effects of noncovalent interactions occurring at sites remote from the reaction center. The IgA preparations hydrolyzed Glu-Ala-Arg-AMC at rates 3-orders of magnitude greater than IgG preparations from the same individuals. The cleavage occurred preferentially on the C terminal side of a basic residue. The activity was confirmed using monoclonal IgAs isolated from patients with multiple myeloma. Active site-directed inhibitors of serine proteases inhibited the catalytic activity and were bound irreversibly by the IgA, suggesting the involvement of a serine protease-like mechanism similar to that utilized by previously described IgM antibodies. These observations suggest that mechanisms underlying B cell clonal selection favor the retention and improvement of catalytic activity in the IgA, but not the IgG compartment of the immune response.
Mitsuda
Yukie
Y
Department of Pathology and Laboratory Medicine, Chemical Immunology Research Center, University of Texas - Houston Medical School, 6431 Fannin, Houston, TX 77030, USA.
Planque
Stephanie
S
Hara
Mariko
M
Kyle
Robert
R
Taguchi
Hiroaki
H
Nishiyama
Yasuhiro
Y
Paul
Sudhir
S
D000595:Amino Acid Sequence; D017151:Antibodies, Catalytic / Q000737:chemistry* / Q000276:immunology / Q000302:isolation & purification; D002384:Catalysis; D003374:Coumarins / Q000737:chemistry; D006801:Humans; D006868:Hydrolysis; D007070:Immunoglobulin A / Q000737:chemistry* / Q000276:immunology / Q000302:isolation & purification; D007074:Immunoglobulin G / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D012463:Saliva / Q000276:immunology; D015842:Serine Proteinase Inhibitors / Q000737:chemistry; D044967:Serum / Q000276:immunology; D013379:Substrate Specificity
D017151:Antibodies, Catalytic; D003374:Coumarins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D010455:Peptides; D015842:Serine Proteinase Inhibitors; C028743:7-amino-4-methylcoumarin