complement c3d


Summary: A 302-amino-acid fragment in the alpha chain (672-1663) of C3b. It is generated when C3b is inactivated (iC3b) and its alpha chain is cleaved by COMPLEMENT FACTOR I into C3c, and C3dg (955-1303) in the presence COMPLEMENT FACTOR H. Serum proteases further degrade C3dg into C3d (1002-1303) and C3g (955-1001).

Top Publications

  1. Bower J, Ross T. A minimum CR2 binding domain of C3d enhances immunity following vaccination. Adv Exp Med Biol. 2006;586:249-64 pubmed
    ..This CR2-binding domain specific 28 amino acid peptide can substitute for the entire C3d molecule and enhance immunity. These results indicate that the adjuvant properties of C3d are associated with CR2 interaction. ..
  2. Gherghiceanu M, Penescu M, Mandache E. The predictive value of peritubular capillaries C3d deposition in IgA glomerulonephritis. J Cell Mol Med. 2005;9:143-52 pubmed
    ..Thus, the predictive value of C3d deposition on PTCs in IgAGN is worth to be taken into consideration as an unfavorable outcome of the disease and request further long run investigations...
  3. Herman J, Lerut E, Van Damme Lombaerts R, Emonds M, Van Damme B. Capillary deposition of complement C4d and C3d in pediatric renal allograft biopsies. Transplantation. 2005;79:1435-40 pubmed
    ..In contrast, C3d(PTC), although highly associated with C4d(PTC), did not correlate with DSA or outcome. ..
  4. Logan G, Wang L, Zheng M, Coppel R, Alexander I. Antigen fusion with C3d3 augments or inhibits humoral immunity to AAV genetic vaccines in a transgene-dependent manner. Immunol Cell Biol. 2010;88:228-32 pubmed publisher
    ..This is the first report to apply the C3d approach to augment responses against a recombinant viral vector system and the consequences of these findings are discussed. ..
  5. Szakonyi G, Guthridge J, Li D, Young K, Holers V, Chen X. Structure of complement receptor 2 in complex with its C3d ligand. Science. 2001;292:1725-8 pubmed
    ..CR2 ligands include complement C3d and Epstein-Barr virus glycoprotein 350/220...
  6. Green T, Montefiori D, Ross T. Enhancement of antibodies to the human immunodeficiency virus type 1 envelope by using the molecular adjuvant C3d. J Virol. 2003;77:2046-55 pubmed
  7. Clark E, Crennell S, Upadhyay A, Zozulya A, Mackay J, Svergun D, et al. A structural basis for Staphylococcal complement subversion: X-ray structure of the complement-binding domain of Staphylococcus aureus protein Sbi in complex with ligand C3d. Mol Immunol. 2011;48:452-62 pubmed publisher
  8. Del Nagro C, Kolla R, Rickert R. A critical role for complement C3d and the B cell coreceptor (CD19/CD21) complex in the initiation of inflammatory arthritis. J Immunol. 2005;175:5379-89 pubmed
    ..These findings indicate that binding of C3d to self-Ags can promote autoimmunity through enhanced Ag retention and presentation by follicular dendritic cells and B cells, respectively. ..
  9. Morikis D, Lambris J. The electrostatic nature of C3d-complement receptor 2 association. J Immunol. 2004;172:7537-47 pubmed

More Information


  1. Haas K, Toapanta F, Oliver J, Poe J, Weis J, Karp D, et al. Cutting edge: C3d functions as a molecular adjuvant in the absence of CD21/35 expression. J Immunol. 2004;172:5833-7 pubmed
    ..Thus, C3d can function as a molecular adjuvant in the absence of CD21/35 expression. ..
  2. Hannan J, Young K, Guthridge J, Asokan R, Szakonyi G, Chen X, et al. Mutational analysis of the complement receptor type 2 (CR2/CD21)-C3d interaction reveals a putative charged SCR1 binding site for C3d. J Mol Biol. 2005;346:845-58 pubmed
    ..However, no difference in C3dg binding relative to wild-type CR2 could be observed for this mutant, suggesting that the dimer may only be found in the crystal form of CR2. ..
  3. Wang L, Oriol Sunyer J, Bello L. Immunogenicity of a bovine viral diarrhea virus E2-C3d fusion protein containing a bovine homolog of C3d. Dev Comp Immunol. 2005;29:907-15 pubmed
    ..The ability of boC3d to function in mice provides a less costly and more convenient animal model than cattle for the preliminary evaluation of E2-boC3d and other bovine antigen-boC3d fusion proteins. ..
  4. Gerl V, Bohl J, Pitz S, Stoffelns B, Pfeiffer N, Bhakdi S. Extensive deposits of complement C3d and C5b-9 in the choriocapillaris of eyes of patients with diabetic retinopathy. Invest Ophthalmol Vis Sci. 2002;43:1104-8 pubmed
    ..Complement activation at this site may evoke a spectrum of pathologic sequelae that could contribute to ocular tissue disease and visual impairment. ..
  5. Cherukuri A, Cheng P, Pierce S. The role of the CD19/CD21 complex in B cell processing and presentation of complement-tagged antigens. J Immunol. 2001;167:163-72 pubmed
    ..The ability of the CD19/CD21 complex to augment processing may be an important element of the mechanism by which the CD19/CD21 complex functions to promote B cell responses to T cell-dependent complement-tagged Ags in vivo. ..
  6. Zanotti G, Bassetto A, Battistutta R, Folli C, Arcidiaco P, Stoppini M, et al. Structure at 1.44 A resolution of an N-terminally truncated form of the rat serum complement C3d fragment. Biochim Biophys Acta. 2000;1478:232-8 pubmed
    ..The truncation at the N-terminus of C3d leads to the exposure of a surface of the molecule that favours dimerisation, so that in both crystal forms, the fragment is present as a dimer, with monomers related by a two-fold axis. ..
  7. Nagar B, Jones R, Diefenbach R, Isenman D, Rini J. X-ray crystal structure of C3d: a C3 fragment and ligand for complement receptor 2. Science. 1998;280:1277-81 pubmed
    ..The structure supports a model whereby the transition of native C3 to its functionally active state involves the disruption of a complementary domain interface and provides insight into the basis for the interaction between C3d and CR2. ..
  8. Delcayre A, Salas F, Mathur S, Kovats K, Lotz M, Lernhardt W. Epstein Barr virus/complement C3d receptor is an interferon alpha receptor. EMBO J. 1991;10:919-26 pubmed
    ..Monoclonal anti-CR2 antibody HB5, but not OKB-7, blocks IFN alpha binding to Raji cells. CR2 or CR2-like molecules may therefore be the major IFN alpha receptors on B lymphocytes. ..
  9. Gierej B, Gornicka B, Wasiutynski A. Role of C3d and C4d complement fragments in the diagnostics of acute allograft rejection after transplantations. Ann Transplant. 2009;14:61-70 pubmed
  10. Haas M, Rahman M, Racusen L, Kraus E, Bagnasco S, Segev D, et al. C4d and C3d staining in biopsies of ABO- and HLA-incompatible renal allografts: correlation with histologic findings. Am J Transplant. 2006;6:1829-40 pubmed
  11. Bower J, Sanders K, Ross T. C3d enhances immune responses using low doses of DNA expressing the HIV-1 envelope from codon-optimized gene sequences. Curr HIV Res. 2005;3:191-8 pubmed
    ..Therefore, both codon-optimization of env sequences and C3d conjugation to Env appear to enhance anti-Env antibodies in an independent and additive manner. ..
  12. Kovacs J, Hannan J, Eisenmesser E, Holers V. Mapping of the C3d ligand binding site on complement receptor 2 (CR2/CD21) using nuclear magnetic resonance and chemical shift analysis. J Biol Chem. 2009;284:9513-20 pubmed publisher
  13. Li K, Okemefuna A, Gor J, Hannan J, Asokan R, Holers V, et al. Solution structure of the complex formed between human complement C3d and full-length complement receptor type 2. J Mol Biol. 2008;384:137-50 pubmed publisher
    ..The implications of these solution results for its immune role are discussed. To our knowledge, this is the first solution structural study of a large multidomain SCR protein CR2 bound to its physiological ligand C3d. ..
  14. Kuypers D, Lerut E, Evenepoel P, Maes B, Vanrenterghem Y, Van Damme B. C3D deposition in peritubular capillaries indicates a variant of acute renal allograft rejection characterized by a worse clinical outcome. Transplantation. 2003;76:102-8 pubmed
    ..In the remaining biopsies, C3d and C4d deposition was found simultaneously. The deposition of complement factor C3d in PTCs indicates a variant type of AR characterized by a worse clinical outcome. ..
  15. Mitchell J, Green T, Bright R, Ross T. Induction of heterosubtypic immunity to influenza A virus using a DNA vaccine expressing hemagglutinin-C3d fusion proteins. Vaccine. 2003;21:902-14 pubmed
    ..The HA-mC3d(3)-DNA vaccinated mice were protected from heterologous influenza challenge, even though sera from these mice had no viral-neutralizing activity against heterologous virus. ..
  16. Zhang D, Xia Q, Wu J, Liu D, Wang X, Niu Z. Construction and immunogenicity of DNA vaccines encoding fusion protein of murine complement C3d-p28 and GP5 gene of porcine reproductive and respiratory syndrome virus. Vaccine. 2011;29:629-35 pubmed publisher
    ..This approach may provide a new strategy for the development of efficient vaccines against the PRRSV for pigs in the future. ..
  17. Bower J, Green T, Ross T. DNA vaccines expressing soluble CD4-envelope proteins fused to C3d elicit cross-reactive neutralizing antibodies to HIV-1. Virology. 2004;328:292-300 pubmed
    ..The fusion of sCD4 to the HIV-1 envelope exposes neutralizing epitopes that elicit broad protective immunity when the fusion complex is coupled with the molecular adjuvant, C3d. ..
  18. Toapanta F, Ross T. Mouse strain-dependent differences in enhancement of immune responses by C3d. Vaccine. 2004;22:1773-81 pubmed
    ..In addition, the avidity maturation of the anti-Env antisera was enhanced in outbred mice with DNA expressing sgp120-mC3d. Overall, C3d conjugated DNA vaccines elicited enhanced immune responses in outbred mice compared to inbred mice. ..
  19. Shaw C, Storek M, Young K, Kovacs J, Thurman J, Holers V, et al. Delineation of the complement receptor type 2-C3d complex by site-directed mutagenesis and molecular docking. J Mol Biol. 2010;404:697-710 pubmed publisher
  20. Hellwage J, Jokiranta T, Friese M, Wolk T, Kampen E, Zipfel P, et al. Complement C3b/C3d and cell surface polyanions are recognized by overlapping binding sites on the most carboxyl-terminal domain of complement factor H. J Immunol. 2002;169:6935-44 pubmed
    ..Mutations in this region, as recently reported in patients with familial hemolytic uremic syndrome, may lead to indiscriminatory C attack against self cells. ..
  21. Mitsuyoshi J, Hu Y, Test S. Role of complement receptor type 2 and endogenous complement in the humoral immune response to conjugates of complement C3d and pneumococcal serotype 14 capsular polysaccharide. Infect Immun. 2005;73:7311-6 pubmed
    ..Thus, the adjuvant effect of C3d conjugated to PPS14 requires C3d-CR2 interactions, does not require activation of endogenous complement, and is not mediated by TD carrier effects. ..
  22. Kieslich C, Morikis D. The two sides of complement C3d: evolution of electrostatics in a link between innate and adaptive immunity. PLoS Comput Biol. 2012;8:e1002840 pubmed publisher
    ..methods to identify regions of evolutionarily conserved electrostatic potential based on 24 homologues of complement C3d and 4 homologues of CR2...
  23. Ross T, Xu Y, Bright R, Robinson H. C3d enhancement of antibodies to hemagglutinin accelerates protection against influenza virus challenge. Nat Immunol. 2000;1:127-31 pubmed
    ..They also correlated to complete protection from live virus challenge by a single vaccination at a dose ten times lower than the protective dose for non-C3d forms of HA. ..
  24. Haspel N, Ricklin D, Geisbrecht B, Kavraki L, Lambris J. Electrostatic contributions drive the interaction between Staphylococcus aureus protein Efb-C and its complement target C3d. Protein Sci. 2008;17:1894-906 pubmed publisher
    ..We also characterized other key interactions along the Efb-C/C3d binding interface and found an intricate network of salt bridges and hydrogen bonds that anchor Efb-C to C3d, resulting in its potent complement inhibitory properties. ..
  25. Mkrtichyan M, Ghochikyan A, Movsesyan N, Karapetyan A, Begoyan G, Yu J, et al. Immunostimulant adjuvant patch enhances humoral and cellular immune responses to DNA immunization. DNA Cell Biol. 2008;27:19-24 pubmed
    ..We have combined an influenza DNA vaccine, hemagglutinin fused with three copies of complement C3d, to enhance uptake and antigen presentation, with an IS patch containing heat-labile enterotoxin from ..
  26. Toapanta F, Ross T. Complement-mediated activation of the adaptive immune responses: role of C3d in linking the innate and adaptive immunity. Immunol Res. 2006;36:197-210 pubmed
  27. Ricklin D, Ricklin Lichtsteiner S, Markiewski M, Geisbrecht B, Lambris J. Cutting edge: members of the Staphylococcus aureus extracellular fibrinogen-binding protein family inhibit the interaction of C3d with complement receptor 2. J Immunol. 2008;181:7463-7 pubmed
    ..Our study therefore suggests that S. aureus may disrupt both the innate and adaptive immune responses with a single protein module. ..
  28. Test S, Mitsuyoshi J, Connolly C, Lucas A. Increased immunogenicity and induction of class switching by conjugation of complement C3d to pneumococcal serotype 14 capsular polysaccharide. Infect Immun. 2001;69:3031-40 pubmed
    ..As a means of harnessing the adjuvant potential of the innate immune system, C3d conjugates may prove useful as a component of vaccines against encapsulated bacteria. ..
  29. Isenman D, Leung E, Mackay J, Bagby S, van den Elsen J. Mutational analyses reveal that the staphylococcal immune evasion molecule Sbi and complement receptor 2 (CR2) share overlapping contact residues on C3d: implications for the controversy regarding the CR2/C3d cocrystal structure. J Immunol. 2010;184:1946-55 pubmed publisher
    ..The results with CR2 confirm our earlier mapping studies and cast even further doubt on the physiologic relevance of the complex visualized in the C3d:CR2 cocrystal. ..
  30. Bower J, Yang X, Sodroski J, Ross T. Elicitation of neutralizing antibodies with DNA vaccines expressing soluble stabilized human immunodeficiency virus type 1 envelope glycoprotein trimers conjugated to C3d. J Virol. 2004;78:4710-9 pubmed
    ..Therefore, DNA vaccines expressing trimeric envelopes coupled to mC3d, expressed in vivo from codon-optimized sequences, elicit low titers of neutralizing antibodies against primary isolates of HIV-1. ..
  31. Liu G, Lan J, Chuai X, Gao Z, Jin Y, Zhang Y, et al. [Immune effects of four coxsackievirus B3 VP1 DNA fusion vaccines in mice]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2010;26:103-6 pubmed
    ..Both pcDNA3/MDC-VP1 and pcDNA3/VP1-C3d3 vaccines could induce stronger immune responses, resulting in higher survival rates and better protective effects on CVB3 infection than pcDNA3/STxB-VP1, pcDNA3/mBD2-VP1 and pcDNA3/VP1 vaccines. ..
  32. Abdel Latif M, Abdel Moneim A, El Hefnawy M, Khalil R. Comparative and correlative assessments of cytokine, complement and antibody patterns in paediatric type 1 diabetes. Clin Exp Immunol. 2017;190:110-121 pubmed publisher
    ..In conclusion, IFN-?, IL-12 and IL-17 played an essential role in exacerbating EV+ -T1D, while C3d, sC5b -9, IL-10 and -20 displayed distinct patterns. ..
  33. McGeer P, Akiyama H, Itagaki S, McGeer E. Activation of the classical complement pathway in brain tissue of Alzheimer patients. Neurosci Lett. 1989;107:341-6 pubmed
    ..Properdin and fraction Bb of factor B, two proteins that bind to tissue when the alternative complement pathway is activated, were not detected immunohistochemically. ..
  34. Ray D, Subramanyam S, Krishna S, Ramanathan V. Serum C3d levels in tropical pulmonary eosinophilia. Indian J Med Res. 2010;131:555-8 pubmed
    ..Absence of significant change in serum C3d goes against the possibility of complement activation in TPE. Results of our study suggest that complement system is unlikely to play a pivotal role in pathogenesis of TPE. ..
  35. Ross R, Zhou M, Shen D, Fariss R, Ding X, Bojanowski C, et al. Immunological protein expression profile in Ccl2/Cx3cr1 deficient mice with lesions similar to age-related macular degeneration. Exp Eye Res. 2008;86:675-83 pubmed publisher
    ..Immunohistochemistry revealed increased complement C3d in Bruch's membrane, retinal pigment epithelium (RPE), choroidal capillaries, and particularly drusen of the ..
  36. Inoue T, Yamakawa M, Takahashi T. Expression of complement regulating factors in gastric cancer cells. Mol Pathol. 2002;55:193-9 pubmed
    ..These data indicate that DAF may play a role in cancer cell infiltration and resistance in tumour cells. ..
  37. Sasajima T, Watanabe H, Sato S, Sato Y, Ohira H. Anti-triosephosphate isomerase antibodies in cerebrospinal fluid are associated with neuropsychiatric lupus. J Neuroimmunol. 2006;181:150-6 pubmed
    ..Our results suggest that anti-TPI form IC in CSF and contribute to the pathogenesis of neuropsychiatric lupus by activating the complement system. ..
  38. Duce J, Hollander W, Jaffe R, Abraham C. Activation of early components of complement targets myelin and oligodendrocytes in the aged rhesus monkey brain. Neurobiol Aging. 2006;27:633-44 pubmed
    ..Taken together the findings support the concept that activation of early components of complement in the brain may be a normal biological process that involves the metabolism of myelin and oligodendrocytes and up-regulates with age. ..
  39. Gonzalez Stawinski G, Tan C, Smedira N, Starling R, Rodriguez E. Decay-accelerating factor expression may provide immunoprotection against antibody-mediated cardiac allograft rejection. J Heart Lung Transplant. 2008;27:357-61 pubmed publisher
    ..Expression of DAF on cardiac allografts may provide an immunoprotective mechanism against the deleterious effects of complement deposition in patients with antibody-mediated cardiac allograft rejection. ..
  40. Fujita Y, Yamaguchi S, Kakino A, Iwamoto S, Yoshimoto R, Sawamura T. Lectin-like oxidized LDL receptor 1 is involved in CRP-mediated complement activation. Clin Chem. 2011;57:1398-405 pubmed publisher
    ..LOX-1 appears to be involved in CRP-induced complement activation, and thus may serve to locate the site of CRP-induced complement activation and inflammation. ..
  41. Kajander T, Lehtinen M, Hyvärinen S, Bhattacharjee A, Leung E, Isenman D, et al. Dual interaction of factor H with C3d and glycosaminoglycans in host-nonhost discrimination by complement. Proc Natl Acad Sci U S A. 2011;108:2897-902 pubmed publisher
    ..This explains the molecular basis of atypical hemolytic uremic syndrome, where mutations on the binding interfaces between FH19-20 and C3d or between FH20 and glycosaminoglycans lead to complement attack against host surfaces. ..
  42. Pedersen E, Frøyland E, Kvissel A, Pharo A, Skålhegg B, Rootwelt T, et al. Expression of complement regulators and receptors on human NT2-N neurons--effect of hypoxia and reoxygenation. Mol Immunol. 2007;44:2459-68 pubmed
    ..The cells may respond to locally produced C3a and, at the same time, be well protected against complement attack. Although severe hypoxia-reoxygenation may down-regulate CD55 expression, it does not seem to influence C3d-deposition. ..
  43. Chaudhary R, Das S, Gupta R, Khetan D. Application of flow cytometry in detection of red-cell-bound IgG in Coombs-negative AIHA. Hematology. 2006;11:295-300 pubmed
    ..We conclude that FC is more sensitive test than the CTT and helps in the serological diagnosis of Coombs negative AIHA. However, in resource poor settings, GT DAT can be a good alternative to FC. ..
  44. Magro C, Abbas A, Seilstad K, Pope Harman A, Nadasdy T, Ross P. C3d and the septal microvasculature as a predictor of chronic lung allograft dysfunction. Hum Immunol. 2006;67:274-83 pubmed
    ..C3d by IH manifests higher sensitivity but similar specificity compared to C3d by IIF. ..
  45. Breukels M, Zandvoort A, Rijkers G, Lodewijk M, Klok P, Harms G, et al. Complement dependency of splenic localization of pneumococcal polysaccharide and conjugate vaccines. Scand J Immunol. 2005;61:322-8 pubmed
    ..These basic findings may explain the effectiveness of conjugated vaccines in young children and may open the way for their application in other patient groups. ..
  46. Gilbert H, Eaton J, Hannan J, Holers V, Perkins S. Solution structure of the complex between CR2 SCR 1-2 and C3d of human complement: an X-ray scattering and sedimentation modelling study. J Mol Biol. 2005;346:859-73 pubmed
    ..We conclude that the open V-shaped structures formed by CR2 SCR 1-2, both when free and when bound to C3d, are optimal for the formation of a tight two-domain interaction with its ligand C3d. ..
  47. Li D, Wang H, Li L, Zhao X, Wang M, Zhu Y, et al. Gene fusion of molecular adjuvant C3d to hCGbeta enhances the anti-hCGbeta antibody response in DNA immunization. J Reprod Immunol. 2003;60:129-41 pubmed
    ..The C3d3 molecular adjuvant can enhance significantly the immunogenecity of hCGbeta antigen in DNA immunization. ..
  48. Hannan J, Young K, Szakonyi G, Overduin M, Perkins S, Chen X, et al. Structure of complement receptor (CR) 2 and CR2-C3d complexes. Biochem Soc Trans. 2002;30:983-9 pubmed
    ..To characterize this interaction further, several approaches directed at the determination of solution phase interactions as well as the analysis of the three-dimensional structure of CR2 alone and key CR2 mutants will be necessary. ..
  49. Hollyfield J, Bonilha V, Rayborn M, Yang X, Shadrach K, Lu L, et al. Oxidative damage-induced inflammation initiates age-related macular degeneration. Nat Med. 2008;14:194-8 pubmed publisher
    ..This new model provides a platform for dissecting the molecular pathology of oxidative damage in the outer retina and the immune response contributing to AMD...
  50. Mattsson P, Morgan B, Svensson M. Complement activation and CD59 expression in the motor facial nucleus following intracranial transection of the facial nerve in the adult rat. J Neuroimmunol. 1998;91:180-9 pubmed
    ..We propose a neuroprotective role for the complement regulators CD59 and clusterin against homologous attack of complement to facial motor neurons. ..
  51. Smith G, Nagar B, Rini J, Hauptman H, Blessing R. The use of SnB to determine an anomalous scattering substructure. Acta Crystallogr D Biol Crystallogr. 1998;54:799-804 pubmed
    ..Higher success rates with SnB were observed for the 2.0 A peak and edge diffE data. ..
  52. Koch M, Frazier J, Sodroski J, Wyatt R. Characterization of antibody responses to purified HIV-1 gp120 glycoproteins fused with the molecular adjuvant C3d. Virology. 2005;340:277-84 pubmed
  53. Leung V, Yun S, Botto M, Mason J, Malik T, Song W, et al. Decay-accelerating factor suppresses complement C3 activation and retards atherosclerosis in low-density lipoprotein receptor-deficient mice. Am J Pathol. 2009;175:1757-67 pubmed publisher
    ..Because upstream complement activation is potentially protective, this study underlines the importance of DAF in shielding the arterial wall from the atherogenic effects of complement...