THE STRUCTURAL BASIS OF GERMLINE-ENCODED V(H)3 IMMUNOGLOBULIN BINDING TO STAPHYLOCOCCAL PROTEIN-A

被引:114
作者
HILLSON, JL [1 ]
KARR, NS [1 ]
OPPLIGER, IR [1 ]
MANNIK, M [1 ]
SASSO, EH [1 ]
机构
[1] UNIV WASHINGTON, DIV RHEUMATOL, SEATTLE, WA 98195 USA
关键词
D O I
10.1084/jem.178.1.331
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The ability of human V(H)3 immunoglobulins (Ig) to bind to staphylococcal protein A (SPA) via their Fab region is analogous to the binding of bacterial superantigens to T cell receptors. The present report establishes the structural basis for the interaction of SPA and V(H)3 Ig. We have studied a panel of 27 human monoclonal IgM that were derived from fetal B lymphocytes. As such, these IgM were expected to be encoded by unmutated germline genes. Binding to SPA in ELISA occurred with 15 of 15 V(H)3 IgM, but none of 12 IgM from the V(H)1, V(H)4, V(H)5, or V(H)6 families. The V(H) sequences of the 27 IgM were derived from 20 distinct V(H) elements, including 11 from the V(H)3 family. Use of D, J(H), and C(L) genes was similar among V(H)3 and non-V(H)3 IgM. A comparison of the corresponding V(H) protein sequences, and those of previously studied IgM, identified a probable site for SPA binding that includes V(H)3 residues in framework region 3 (FR3), and perhaps FR1 and 3' complementary determining region 2. The results thus demonstrate that among human IgM, specificity for SPA is encoded by at least 11 different V(H)3 germline genes. Furthermore, like the T cell superantigens, SPA likely binds to residues in the V(H) framework region, outside the classical antigen-binding site of the hypervariable loops.
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页码:331 / 336
页数:6
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