Differential complement activation by bovine IgG2 allotypes.
Immunoglobulin allotypes and complement (C) are known to be related to susceptibility to infection. Because bovine IgG2 is important in resistance to pyogenic infections and because its two allotypes, IgG2a and IgG2b, differ in sequence in the CH1, hinge, CH2, and CH3 regions, we tested the ability of these allotypes to initiate the bovine C cascade. Bovine IgG2a and IgG2b were standardized according to specific anti guinea pig red blood cell (GPRBC) ELISA activity using anti IgG2 reagents shown essentially unbiased for allotype. Complement activating activity of the allotypes was quantitated in a GPRBC lysis assay. With this system, IgG2b consistently had more than twice the activity in bovine C mediated lysis as compared with IgG2a. The fact that both EDTA and EGTA/Mg almost completely inhibited C mediated lysis of GPRBCs indicated that lysis was due to the classical pathway. Since antibody usually activates C by the classical pathway, this supports the supposition that activation was by the IgG2-GPRBC complexes. Flexibility analyses showed that IgG2b had a more rigid hinge than IgG2a, perhaps partially explaining the greater efficiency of IgG2b in C activation. Other mechanisms may include differences in glycosylation and in the amino acid at position 332. The difference in ability to activate C may mean that animals of the IgG2a allotype could be more susceptible to infection with extracellular pyogenic pathogens which are killed by C or by phagocytes after opsonization with IgG2 and C.
Bastida-Corcuera
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FD
Department of Pathology, School of Medicine, University of California, San Diego 92103-8416, USA.
Butler
J E
JE
Yahiro
S
S
Corbeil
L B
LB
D000818:Animals; D000911:Antibodies, Monoclonal; D002417:Cattle / Q000276:immunology*; D002614:Chelating Agents / Q000737:chemistry; D002848:Chromatography, DEAE-Cellulose / Q000662:veterinary; D003171:Complement Pathway, Classical / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000662:veterinary; D006168:Guinea Pigs; D007126:Immunoglobulin Allotypes / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D015999:Multivariate Analysis; D013499:Surface Properties
D000911:Antibodies, Monoclonal; D002614:Chelating Agents; D007126:Immunoglobulin Allotypes; D007074:Immunoglobulin G; D003165:Complement System Proteins