MONOCLONAL IGM RHEUMATOID FACTORS BIND IGG AT A DISCONTINUOUS EPITOPE COMPRISED OF AMINO-ACID LOOPS FROM HEAVY-CHAIN CONSTANT-REGION DOMAIN-2 AND DOMAIN-3

被引:54
作者
ARTANDI, SE
CALAME, KL
MORRISON, SL
BONAGURA, VR
机构
[1] COLUMBIA UNIV COLL PHYS & SURG,DEPT MICROBIOL,NEW YORK,NY 10032
[2] UNIV CALIF LOS ANGELES,INST MOLEC BIOL,DEPT MICROBIOL & MOLEC GENET,LOS ANGELES,CA 90024
[3] ALBERT EINSTEIN COLL MED,LONG ISL JEWISH MED CTR,SCHNEIDER CHILDRENS HOSP,DEPT PEDIAT,NEW HYDE PK,NY 11042
关键词
AUTOANTIBODY; ANTIBODY STRUCTURE; RHEUMATOID ARTHRITIS;
D O I
10.1073/pnas.89.1.94
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
A combination of site-directed mutagenesis and exon exchange has been used to further define the structure on IgG recognized by monoclonal IgM rheumatoid factors (RFs) from patients with Waldenstrom macroglobulinemia. Most of these RFs bound IgG1, -2, and -4 but not IgG3. For these RFs, His-435 is a critical residue for binding and replacing it with arginine, the residue present in IgG3, destroys or reduces RF binding. However, additional polymorphic sequences in both the heavy-chain constant-region domains (C(H)) 2 and 3 are important for RF binding. Among the important residues in C(H)2 are amino acids 252-254 and 309-311, which are conserved among IgG isotypes and comprise two loops of amino acids on the surface of the domain. Therefore, at least three regions, two from C(H)2 and One from C(H)3, contribute significantly to the epitope recognized by the RFs. Although this epitope contains many of the same residues as the staphylococcal protein A binding site on IgG, the binding specificities of staphylococcal protein A and monoclonal RFs are not identical. Sera from patients with rheumatoid arthritis contain antibodies directed not only at this epitope but also at other sites on IgG.
引用
收藏
页码:94 / 98
页数:5
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