Characterization of human complement receptor type 2 (CR2/CD21) as a receptor for IFN-α: A potential role in systemic lupus erythematosus

Rengasamy Asokan, Jing Hua, Kendra A. Young, Hannah J. Gould, Jonathan P. Hannan, Damian M. Kraus, G. Szakonyi, Gabrielle J. Grundy, Xiaojiang S. Chen, Mary K. Crow, V. Michael Holers

Research output: Contribution to journalArticle

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Abstract

Human complement receptor type 2 (CR2/CD21) is a B lymphocyte membrane glycoprotein that plays a central role in the immune responses to foreign Ags as well as the development of autoimmunity to nuclear Ags in systemic lupus erythematosus. In addition to these three well-characterized ligands, C3d/iC3b, EBV-gp350, and CB23, a previous study has identified CR2 as a potential receptor for IFN-α. IFN-α, a multifunctional cytokine important in the innate immune system, lias recently been proposed to play a major pathogenic role in the development of systemic lupus erythematosus in humans and mice. In this study, we have shown using surface plasmon resonance and ELISA approaches that CR2 will bind IFN-α in the same affinity range as the other three well-characterized ligands studied in parallel. In addition, we show that IFN-α interacts with short consensus repeat domains 1 and 2 in a region that serves as the ligand binding site for C3d/iC3b, EBV-gp350, and CD23. Finally, we show that treatment of purified human peripheral blood B cells with the inhibitory anti-CR2 mAb 171 diminishes the induction of IFN-α- responsive genes. Thus, IFN-α represents a fourth class of extracellular ligands for CR2 and interacts with the same domain as the other three ligands. Defining the role of CR2 as compared with the well-characterized type 1 IFN-α receptor 1 and 2 in mediating innate immune and autoimmune roles of this cytokine should provide additional insights into the biologic roles of this interaction.

Original languageEnglish
Pages (from-to)383-394
Number of pages12
JournalJournal of Immunology
Volume177
Issue number1
Publication statusPublished - Jul 1 2006

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Complement 3d Receptors
Systemic Lupus Erythematosus
Ligands
Complement C3b
Human Herpesvirus 4
B-Lymphocytes
Cytokines
Surface Plasmon Resonance
Membrane Glycoproteins
Autoimmunity
Immune System
Blood Cells
Enzyme-Linked Immunosorbent Assay
Binding Sites
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

Asokan, R., Hua, J., Young, K. A., Gould, H. J., Hannan, J. P., Kraus, D. M., ... Holers, V. M. (2006). Characterization of human complement receptor type 2 (CR2/CD21) as a receptor for IFN-α: A potential role in systemic lupus erythematosus. Journal of Immunology, 177(1), 383-394.

Characterization of human complement receptor type 2 (CR2/CD21) as a receptor for IFN-α : A potential role in systemic lupus erythematosus. / Asokan, Rengasamy; Hua, Jing; Young, Kendra A.; Gould, Hannah J.; Hannan, Jonathan P.; Kraus, Damian M.; Szakonyi, G.; Grundy, Gabrielle J.; Chen, Xiaojiang S.; Crow, Mary K.; Holers, V. Michael.

In: Journal of Immunology, Vol. 177, No. 1, 01.07.2006, p. 383-394.

Research output: Contribution to journalArticle

Asokan, R, Hua, J, Young, KA, Gould, HJ, Hannan, JP, Kraus, DM, Szakonyi, G, Grundy, GJ, Chen, XS, Crow, MK & Holers, VM 2006, 'Characterization of human complement receptor type 2 (CR2/CD21) as a receptor for IFN-α: A potential role in systemic lupus erythematosus', Journal of Immunology, vol. 177, no. 1, pp. 383-394.
Asokan, Rengasamy ; Hua, Jing ; Young, Kendra A. ; Gould, Hannah J. ; Hannan, Jonathan P. ; Kraus, Damian M. ; Szakonyi, G. ; Grundy, Gabrielle J. ; Chen, Xiaojiang S. ; Crow, Mary K. ; Holers, V. Michael. / Characterization of human complement receptor type 2 (CR2/CD21) as a receptor for IFN-α : A potential role in systemic lupus erythematosus. In: Journal of Immunology. 2006 ; Vol. 177, No. 1. pp. 383-394.
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