Human complement receptor 2 (CR2/CD21) as a receptor for DNA

Implications for its roles in the immune response and the pathogenesis of systemic lupus erythematosus (SLE)

Rengasamy Asokan, Nirmal K. Banda, G. Szakonyi, Xiaojiang S. Chen, V. Michael Holers

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Human CR2 is a B cell membrane glycoprotein that plays a central role in autoimmunity. Systemic lupus erythematosus (SLE) patients show reduced CR2 levels, and complete deficiency of CR2 and CR1 promotes the development of anti-DNA antibodies in mouse models of SLE. Here we show that multiple forms of DNA, including bacterial, viral and mammalian DNA, bind to human CR2 with moderately high affinity. Surface plasmon resonance studies showed that methylated DNA bound with high affinity with CR2 at a maximal KD of 6nM. DNA was bound to the first two domains of CR2 and this binding was blocked by using a specific inhibitory anti-CR2 mAb. DNA immunization in Cr2-/- mice revealed a specific defect in immune responses to bacterial DNA. CR2 can act as a receptor for DNA in the absence of complement C3 fixation to this ligand. These results suggest that CR2 plays a role in the recognition of foreign DNA during host-immune responses. This recognition function of CR2 may be a mechanism that influences the development of autoimmunity to DNA in SLE.

Original languageEnglish
Pages (from-to)99-110
Number of pages12
JournalMolecular Immunology
Volume53
Issue number1-2
DOIs
Publication statusPublished - Jan 2013

Fingerprint

Complement 3d Receptors
Systemic Lupus Erythematosus
DNA
Bacterial DNA
Autoimmunity
Complement C3
Surface Plasmon Resonance
Antinuclear Antibodies
Membrane Glycoproteins
Viral DNA
Immunization
B-Lymphocytes
Cell Membrane
DNA receptor
Ligands

Keywords

  • Autoimmunity
  • B lymphocyte
  • Complement receptor 2
  • DNA receptor
  • Protein-DNA interactions
  • Surface plasmon resonance

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology

Cite this

Human complement receptor 2 (CR2/CD21) as a receptor for DNA : Implications for its roles in the immune response and the pathogenesis of systemic lupus erythematosus (SLE). / Asokan, Rengasamy; Banda, Nirmal K.; Szakonyi, G.; Chen, Xiaojiang S.; Holers, V. Michael.

In: Molecular Immunology, Vol. 53, No. 1-2, 01.2013, p. 99-110.

Research output: Contribution to journalArticle

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