Localization of the binding site for the monocyte immunoglobulin (Ig) A- Fc receptor (CD89) to the domain boundary between Calpha2 and Calpha3 in human IgA1

doi:10.1084/jem.183.4.1579

This Article

	Full Text (PDF)
	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 Carayannopoulos, L.
	Articles by Capra, J. D.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Carayannopoulos, L.
	Articles by Capra, J. D.


Social Bookmarking

	What's this?

ARTICLES

Localization of the binding site for the monocyte immunoglobulin (Ig) A- Fc receptor (CD89) to the domain boundary between Calpha2 and Calpha3 in human IgA1

L Carayannopoulos, JM Hexham and JD Capra
Program in Molecular Biophysics, The Molecular Immunology Center, University of Texas Southwestern Medical Center, Dallas, 75235-9140, USA.

Immunoglobulin (Ig) A serves as the first line of humoral defense at all mucosal surfaces and is present in large quantities of blood. In playing its role in humoral immunity, IgA interacts with a variety of effector molecules present both in serum and on the surfaces of immune and inflammatory cells. To study these interactions, we previously established expression of human IgA1 in insect cells using recombinant baculoviruses and showed that the expressed antibody is a structurally and functionally intact polypeptide useful for examining the molecular properties of IgA. Indeed, since the C alpha 2 N-linked glycosylation site lies near the Fab-distal pole of C alpha 2, the inability of a mutant IgA1 lacking C alpha 2 N-glycosylation to bind its cognate receptor suggested that the monocyte Fc alpha receptor (mFcalphaR) recognizes IgA at a hinge-distal site encompassing the boundary between the C alpha 2 and C alpha 3 domains. In this report, we utilize both domain-swapped IgA/IgG and point-mutated IgA chimeras to verify the above hypothesis. Using an antigen-specific rosetting assay and a mFc alpha R-expressing cell line, we show that (a) C alpha 2 and C alpha 3 together are necessary and sufficient for binding; (b) neither the IgA hinge nor the tailpiece is necessary for binding; (c) mutations away from the interdomain boundary do not affect binding; and (d) mutations located near the three-dimensional boundary between C alpha 2 and C alpha 3 completely disrupt binding. Taken together, these results localize the mFc alpha R recognition site on IgA to the boundary region between the second and third constant domains--a site analogous to that recognized by Staphylococcus aureus protein A on IgG. The use of this hinge-distal site is, to date, unique among Fc receptors of the Ig superfamily.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

Ramsland, P. A., Willoughby, N., Trist, H. M., Farrugia, W., Hogarth, P. M., Fraser, J. D., Wines, B. D. (2007). Structural basis for evasion of IgA immunity by Staphylococcus aureus revealed in the complex of SSL7 with Fc of human IgA1. Proc. Natl. Acad. Sci. USA 104: 15051-15056 [Abstract] [Full Text]
Wu, J., Ji, C., Xie, F., Langefeld, C. D., Qian, K., Gibson, A. W., Edberg, J. C., Kimberly, R. P. (2007). Fc{alpha}RI (CD89) Alleles Determine the Proinflammatory Potential of Serum IgA. J. Immunol. 178: 3973-3982 [Abstract] [Full Text]
Senior, B. W., Woof, J. M. (2006). Sites in the CH3 Domain of Human IgA1 That Influence Sensitivity to Bacterial IgA1 Proteases. J. Immunol. 177: 3913-3919 [Abstract] [Full Text]
Wines, B. D., Willoughby, N., Fraser, J. D., Hogarth, P. M. (2006). A Competitive Mechanism for Staphylococcal Toxin SSL7 Inhibiting the Leukocyte IgA Receptor, Fc{alpha}RI, Is Revealed by SSL7 Binding at the C{alpha}2/C{alpha}3 Interface of IgA. J. Biol. Chem. 281: 1389-1393 [Abstract] [Full Text]
Lewis, M. J., Pleass, R. J., Batten, M. R., Atkin, J. D., Woof, J. M. (2005). Structural Requirements for the Interaction of Human IgA with the Human Polymeric Ig Receptor. J. Immunol. 175: 6694-6701 [Abstract] [Full Text]
Langley, R., Wines, B., Willoughby, N., Basu, I., Proft, T., Fraser, J. D. (2005). The Staphylococcal Superantigen-Like Protein 7 Binds IgA and Complement C5 and Inhibits IgA-Fc{alpha}RI Binding and Serum Killing of Bacteria. J. Immunol. 174: 2926-2933 [Abstract] [Full Text]
Ding, Y., Xu, G., Yang, M., Yao, M., Gao, G. F., Wang, L., Zhang, W., Rao, Z. (2003). Crystal Structure of the Ectodomain of Human Fc{alpha}RI. J. Biol. Chem. 278: 27966-27970 [Abstract] [Full Text]
Almogren, A., Senior, B. W., Loomes, L. M., Kerr, M. A. (2003). Structural and Functional Consequences of Cleavage of Human Secretory and Human Serum Immunoglobulin A1 by Proteinases from Proteusmirabilis and Neisseriameningitidis. Infect. Immun. 71: 3349-3356 [Abstract] [Full Text]
Batten, M. R., Senior, B. W., Kilian, M., Woof, J. M. (2003). Amino Acid Sequence Requirements in the Hinge of Human Immunoglobulin A1 (IgA1) for Cleavage by Streptococcal IgA1 Proteases. Infect. Immun. 71: 1462-1469 [Abstract] [Full Text]
van Spriel, A. B., Leusen, J. H. W., Vile, H., van de Winkel, J. G. J. (2002). Mac-1 (CD11b/CD18) as Accessory Molecule for Fc{alpha}R (CD89) Binding of IgA. J. Immunol. 169: 3831-3836 [Abstract] [Full Text]
Mantis, N. J., Cheung, M. C., Chintalacharuvu, K. R., Rey, J., Corthesy, B., Neutra, M. R. (2002). Selective Adherence of IgA to Murine Peyer's Patch M Cells: Evidence for a Novel IgA Receptor. J. Immunol. 169: 1844-1851 [Abstract] [Full Text]
van der Boog, P. J. M., van Zandbergen, G., de Fijter, J. W., Klar-Mohamad, N., van Seggelen, A., Brandtzaeg, P., Daha, M. R., van Kooten, C. (2002). Fc{alpha}RI/CD89 Circulates in Human Serum Covalently Linked to IgA in a Polymeric State. J. Immunol. 168: 1252-1258 [Abstract] [Full Text]
Morton, H. C., Howard, C. J., Storset, A. K., Brandtzaeg, P. (2001). Identification of Residues within the Extracellular Domain 1 of Bovine Fcgamma 2R Essential for Binding Bovine IgG2. J. Biol. Chem. 276: 47794-47800 [Abstract] [Full Text]
Vidarsson, G., van der Pol, W.-L., van den Elsen, J. M. H., Vile, H., Jansen, M., Duijs, J., Morton, H. C., Boel, E., Daha, M. R., Corthesy, B., van de Winkel, J. G. J. (2001). Activity of Human IgG and IgA Subclasses in Immune Defense Against Neisseria meningitidis Serogroup B. J. Immunol. 166: 6250-6256 [Abstract] [Full Text]
Honorio-França, A. C., Launay, P., Carneiro-Sampaio, M. M. S., Monteiro, R. C. (2001). Colostral neutrophils express Fc{alpha} receptors (CD89) lacking {gamma} chain association and mediate noninflammatory properties of secretory IgA. J. Leukoc. Biol. 69: 289-296 [Abstract] [Full Text]
Wines, B. D., Sardjono, C. T., Trist, H. M., Lay, C.-S., Hogarth, P. M. (2001). The Interaction of Fc{{alpha}}RI with IgA and Its Implications for Ligand Binding by Immunoreceptors of the Leukocyte Receptor Cluster. J. Immunol. 166: 1781-1789 [Abstract] [Full Text]
Phillips-Quagliata, J. M., Patel, S., Han, J.-K., Arakelov, S., Rao, T. D., Shulman, M. J., Fazel, S., Corley, R. B., Everett, M., Klein, M. H., Underdown, B. J., Corthesy, B. (2000). The IgA/IgM Receptor Expressed on a Murine B Cell Lymphoma Is Poly-Ig Receptor. J. Immunol. 165: 2544-2555 [Abstract] [Full Text]
Senior, B. W., Dunlop, J. I., Batten, M. R., Kilian, M., Woof, J. M. (2000). Cleavage of a Recombinant Human Immunoglobulin A2 (IgA2)-IgA1 Hybrid Antibody by Certain Bacterial IgA1 Proteases. Infect. Immun. 68: 463-469 [Abstract] [Full Text]
van Zandbergen, G., Westerhuis, R., Mohamad, N. K., van de Winkel, J. G. J., Daha, M. R., van Kooten, C. (1999). Crosslinking of the Human Fc Receptor for IgA (Fc{alpha}RI/CD89) Triggers FcR {gamma}-Chain-Dependent Shedding of Soluble CD89. J. Immunol. 163: 5806-5812 [Abstract] [Full Text]
Pleass, R. J., Dunlop, J. I., Anderson, C. M., Woof, J. M. (1999). Identification of Residues in the CH2/CH3 Domain Interface of IgA Essential for Interaction with the Human Fcalpha Receptor (Fcalpha R) CD89. J. Biol. Chem. 274: 23508-23514 [Abstract] [Full Text]
Craig Morton, H., van Zandbergen, G., van Kooten, C., Howard, C. J., van de Winkel, J. G.�J., Brandtzaeg, P. (1999). Immunoglobulin-binding Sites of Human Fcalpha RI (CD89) and Bovine Fcgamma 2R Are Located in their Membrane-distal Extracellular Domains. J. Exp. Med. 189: 1715-1722 [Abstract] [Full Text]
Johnsson, E., Areschoug, T., Mestecky, J., Lindahl, G. (1999). An IgA-binding Peptide Derived from a Streptococcal Surface Protein. J. Biol. Chem. 274: 14521-14524 [Abstract] [Full Text]
Launay, P., Patry, C., Lehuen, A., Pasquier, B., Blank, U., Monteiro, R. C. (1999). Alternative Endocytic Pathway for Immunoglobulin A Fc Receptors (CD89) Depends on the Lack of FcRgamma Association and Protects against Degradation of Bound Ligand. J. Biol. Chem. 274: 7216-7225 [Abstract] [Full Text]
Hexham, J. M., White, K. D., Carayannopoulos, L. N., Mandecki, W., Brisette, R., Yang, Y.-S., Capra, J. D. (1999). A Human Immunoglobulin (Ig)A Calpha 3 Domain Motif Directs Polymeric Ig Receptor-mediated Secretion. J. Exp. Med. 189: 747-752 [Abstract] [Full Text]
Wines, B. D., Hulett, M. D., Jamieson, G. P., Trist, H. M., Spratt, J. M., Hogarth, P. M. (1999). Identification of Residues in the First Domain of Human Fc{alpha} Receptor Essential for Interaction with IgA. J. Immunol. 162: 2146-2153 [Abstract] [Full Text]
Mattu, T. S., Pleass, R. J., Willis, A. C., Kilian, M., Wormald, M. R., Lellouch, A. C., Rudd, P. M., Woof, J. M., Dwek, R. A. (1998). The Glycosylation and Structure of Human Serum IgA1, Fab, and Fc Regions and the Role of N-Glycosylation on Fcalpha Receptor Interactions. J. Biol. Chem. 273: 2260-2272 [Abstract] [Full Text]
Pleass, R. J., Areschoug, T., Lindahl, G., Woof, J. M. (2001). Streptococcal IgA-binding Proteins Bind in the Calpha 2-Calpha 3 Interdomain Region and Inhibit Binding of IgA to Human CD89. J. Biol. Chem. 276: 8197-8204 [Abstract] [Full Text]