The structural basis of germline-encoded VH3 immunoglobulin binding to staphylococcal protein A

doi:10.1084/jem.178.1.331

This Article

	Full Text (PDF, 577K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Hillson, J. L.
	Articles by Sasso, E. H.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Hillson, J. L.
	Articles by Sasso, E. H.


Social Bookmarking

	What's this?

ARTICLES

The structural basis of germline-encoded VH3 immunoglobulin binding to staphylococcal protein A

JL Hillson, NS Karr, IR Oppliger, M Mannik and EH Sasso
Division of Rheumatology, University of Washington, Seattle 98195.

The ability of human VH3 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 VH3 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 VH3 IgM, but none of 12 IgM from the VH1, VH4, VH5, or VH6 families. The VH sequences of the 27 IgM were derived from 20 distinct VH elements, including 11 from the VH3 family. Use of D, JH, and CL genes was similar among VH3 and non-VH3 IgM. A comparison of the corresponding VH protein sequences, and those of previously studied IgM, identified a probable site for SPA binding that includes VH3 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 VH3 germline genes. Furthermore, like the T cell superantigens, SPA likely binds to residues in the VH framework region, outside the classical antigen-binding site of the hypervariable loops.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

Ventura, E., Sassi, F., Fossati, S., Parodi, A., Blalock, W., Balza, E., Castellani, P., Borsi, L., Carnemolla, B., Zardi, L. (2009). Use of Uteroglobin for the Engineering of Polyvalent, Polyspecific Fusion Proteins. J. Biol. Chem. 284: 26646-26654 [Abstract] [Full Text]
Stamatopoulos, K., Belessi, C., Moreno, C., Boudjograh, M., Guida, G., Smilevska, T., Belhoul, L., Stella, S., Stavroyianni, N., Crespo, M., Hadzidimitriou, A., Sutton, L., Bosch, F., Laoutaris, N., Anagnostopoulos, A., Montserrat, E., Fassas, A., Dighiero, G., Caligaris-Cappio, F., Merle-Beral, H., Ghia, P., Davi, F. (2007). Over 20% of patients with chronic lymphocytic leukemia carry stereotyped receptors: pathogenetic implications and clinical correlations. Blood 109: 259-270 [Abstract] [Full Text]
Goodyear, C. S., Sugiyama, F., Silverman, G. J. (2006). Temporal and Dose-Dependent Relationships between In Vivo B Cell Receptor-Targeted Proliferation and Deletion-Induced by a Microbial B Cell Toxin. J. Immunol. 176: 2262-2271 [Abstract] [Full Text]
Viau, M., Longo, N. S., Lipsky, P. E., Bjorck, L., Zouali, M. (2004). Specific In Vivo Deletion of B-Cell Subpopulations Expressing Human Immunoglobulins by the B-Cell Superantigen Protein L. Infect. Immun. 72: 3515-3523 [Abstract] [Full Text]
Genovese, A., Borgia, G., Bjorck, L., Petraroli, A., de Paulis, A., Piazza, M., Marone, G. (2003). Immunoglobulin Superantigen Protein L Induces IL-4 and IL-13 Secretion from Human Fc{varepsilon}RI+ Cells Through Interaction with the {kappa} Light Chains of IgE. J. Immunol. 170: 1854-1861 [Abstract] [Full Text]
Genovese, A., Bouvet, J.-P., Florio, G., Lamparter-Schummert, B., Bjorck, L., Marone, G. (2000). Bacterial Immunoglobulin Superantigen Proteins A and L Activate Human Heart Mast Cells by Interacting with Immunoglobulin E. Infect. Immun. 68: 5517-5524 [Abstract] [Full Text]
Graille, M., Stura, E. A., Corper, A. L., Sutton, B. J., Taussig, M. J., Charbonnier, J.-B., Silverman, G. J. (2000). Crystal structure of a Staphylococcus aureus protein A domain complexed with the Fab fragment of a human IgM antibody: Structural basis for recognition of B-cell receptors and superantigen activity. Proc. Natl. Acad. Sci. USA 97: 5399-5404 [Abstract] [Full Text]
Neshat, M. N., Goodglick, L., Lim, K., Braun, J. (2000). Mapping the B cell superantigen binding site for HIV-1 gp120 on a VH3 Ig. Int Immunol 12: 305-312 [Abstract] [Full Text]
Leonetti, M., Galon, J., Thai, R., Sautes-Fridman, C., Moine, G., Menez, A. (1999). Presentation of Antigen in Immune Complexes Is Boosted by Soluble Bacterial Immunoglobulin Binding Proteins. JEM 189: 1217-1228 [Abstract] [Full Text]
Karray, S., Juompan, L., Maroun, R. C., Isenberg, D., Silverman, G. J., Zouali, M. (1998). Structural Basis of the gp120 Superantigen-Binding Site on Human Immunoglobulins. J. Immunol. 161: 6681-6688 [Abstract] [Full Text]
Silverman, G. J., Nayak, J. V., Warnatz, K., Hajjar, F. F., Cary, S., Tighe, H., Curtiss, V. E. (1998). The Dual Phases of the Response to Neonatal Exposure to a VH Family-Restricted Staphylococcal B Cell Superantigen. J. Immunol. 161: 5720-5732 [Abstract] [Full Text]
Zhang, M., Majid, A., Bardwell, P., Vee, C., Davidson, A. (1998). Rheumatoid Factor Specificity of a VH3-Encoded Antibody Is Dependent on the Heavy Chain CDR3 Region and Is Independent of Protein A Binding. J. Immunol. 161: 2284-2289 [Abstract] [Full Text]
Domiati-Saad, R., Lipsky, P. E. (1998). Staphylococcal Enterotoxin A Induces Survival of VH3-Expressing Human B Cells by Binding to the VH Region with Low Affinity. J. Immunol. 161: 1257-1266 [Abstract] [Full Text]
Kozlowski, L. M., Li, W., Goldschmidt, M., Levinson, A. I. (1998). In Vivo Inflammatory Response to a Prototypic B Cell Superantigen: Elicitation of an Arthus Reaction by Staphylococcal Protein A. J. Immunol. 160: 5246-5252 [Abstract] [Full Text]
Bouvet, J.-P., Dighiero, G. (1998). From Natural Polyreactive Autoantibodies to A La Carte Monoreactive Antibodies to Infectious Agents: Is It a Small World after All?. Infect. Immun. 66: 1-4 [Full Text]