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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review

Antigenic Variation

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Disease relevance of Antigenic Variation

  • Differential immunoscreening and RT-PCR demonstrate that IFN-gamma-mediated signals facilitate spirochete recombination at the variable major protein like sequence locus, a site for early antigenic variation in vivo, and that recombination rates by B. burgdorferi N40 are lower in IFN-gammaR-deficient mice than in control animals [1].
  • The antigenic diversity threshold theory predicts that antigenic sites of human immunodeficiency virus type 1, such as the V3 region of the external glycoprotein gp120, evolve more rapidly during the symptom-free period in individuals progressing to AIDS than in those who remain asymptomatic for a long time [2].
  • To define the structure of the caprine arthritis-encephalitis virus (CAEV) env gene and characterize genetic changes which occur during antigenic variation, we sequenced the env genes of CAEV-63 and CAEV-Co, two antigenic variants of CAEV defined by serum neutralization [3].
  • Anaplasma phagocytophilum immunodominant polymorphic major surface protein P44s have been hypothesized to go through antigenic variation, but the within-host dynamics of p44 expression has not been demonstrated [4].
  • The antigenic variation of the relapsing fever agent Borrelia hermsii is associated with changes in the expression of the Vlp and Vsp outer membrane lipoproteins [5].

High impact information on Antigenic Variation

  • The malaria parasite Plasmodium falciparum undergoes antigenic variation to evade host immune responses through switching expression of variant surface proteins encoded by the var gene family [6].
  • F2 more prominently lines the channels and makes the majority of the glycan contacts, underscoring its role in cytoadherence and in antigenic variation in malaria [7].
  • In P. falciparum, subtelomeric domains are conserved and contain ordered arrays of members of multigene families, such as var, rif and stevor, encoding virulence determinants of cytoadhesion and antigenic variation [8].
  • Telomeric reciprocal recombination as a possible mechanism for antigenic variation in trypanosomes [9].
  • Recently, however, IFN-alpha has been found to include at least eight different subtypes, as indicated by measurement of antigenic variability, DNA hybridization and amino acid sequencing [10].

Chemical compound and disease context of Antigenic Variation


Biological context of Antigenic Variation


Anatomical context of Antigenic Variation


Associations of Antigenic Variation with chemical compounds


Gene context of Antigenic Variation

  • The observed pattern of DNA variation in this region is consistent with the selection model developed in this article, suggesting that strong selection might be working to maintain the RHCE/RHD antigen variation in the two-locus system [31].
  • A homologue of the recombination-dependent growth gene, rdgC, is involved in gonococcal pilin antigenic variation [32].
  • Because of the antigenic variation in the serum CEA, markedly different CEA concentrations (varying by three orders of magnitude) were measurable by two different antisera (Roche and Montreal) [33].
  • The outer membrane proteins (OMPs) P1 and P2 of Haemophilus influenzae type b exhibit molecular size and antigenic variation [34].
  • Analysis of antigenic diversity of MSP5 shows a lack of sequence variation between various isolates of P. falciparum from different geographical locations, a feature unusual for surface proteins of merozoites and one that may simplify vaccine formulation [35].

Analytical, diagnostic and therapeutic context of Antigenic Variation

  • Virus neutralization tests performed with sera from experimentally infected salmon indicated that SPDV and SDV belonged to the same serotype; however, antigenic variation was detected among SDV and geographically different SPDV isolates by using monoclonal antibodies [36].
  • The parasites have the ability to escape immune control by two means: by antigenic variation of the surface glycoprotein coat so that waves of variant parasites arise and by inducing a general immunosuppression affecting immune responses to the parasite as well as to parasite-unrelated antigens [37].
  • Assignment of the gene(s) involved in expression of the Meth A antigen to the distal region of chromosome 12, the same region encoding Igh, raised the possibility that genetic elements responsible for antibody idiotype could be involved in the antigenic diversity of tumour-specific transplantation antigens [38].
  • Eighteen Coxiella burnetii strains from a variety of clinical and geographical sources were screened for antigenic variation of polypeptides by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) coupled with Coomassie brilliant blue (CBB) staining or immunoblotting [39].
  • Results illustrate a continued antigenic variation in an endemic area where vaccination has been used; however, asymmetric serological reactions between the A24 vaccine strain and the most recent field isolate indicated that a vaccine incorporating A24 should still give adequate protection [40].


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  2. Intrahost human immunodeficiency virus type 1 evolution is related to length of the immunocompetent period. Lukashov, V.V., Kuiken, C.L., Goudsmit, J. J. Virol. (1995) [Pubmed]
  3. Structure and genetic variability of envelope glycoproteins of two antigenic variants of caprine arthritis-encephalitis lentivirus. Knowles, D.P., Cheevers, W.P., McGuire, T.C., Brassfield, A.L., Harwood, W.G., Stem, T.A. J. Virol. (1991) [Pubmed]
  4. Rapid sequential changeover of expressed p44 genes during the acute phase of Anaplasma phagocytophilum infection in horses. Wang, X., Rikihisa, Y., Lai, T.H., Kumagai, Y., Zhi, N., Reed, S.M. Infect. Immun. (2004) [Pubmed]
  5. In vitro and in vivo neutralization of the relapsing fever agent Borrelia hermsii with serotype-specific immunoglobulin M antibodies. Barbour, A.G., Bundoc, V. Infect. Immun. (2001) [Pubmed]
  6. Heterochromatin silencing and locus repositioning linked to regulation of virulence genes in Plasmodium falciparum. Duraisingh, M.T., Voss, T.S., Marty, A.J., Duffy, M.F., Good, R.T., Thompson, J.K., Freitas-Junior, L.H., Scherf, A., Crabb, B.S., Cowman, A.F. Cell (2005) [Pubmed]
  7. Structural basis for the EBA-175 erythrocyte invasion pathway of the malaria parasite Plasmodium falciparum. Tolia, N.H., Enemark, E.J., Sim, B.K., Joshua-Tor, L. Cell (2005) [Pubmed]
  8. A superfamily of variant genes encoded in the subtelomeric region of Plasmodium vivax. del Portillo, H.A., Fernandez-Becerra, C., Bowman, S., Oliver, K., Preuss, M., Sanchez, C.P., Schneider, N.K., Villalobos, J.M., Rajandream, M.A., Harris, D., Pereira da Silva, L.H., Barrell, B., Lanzer, M. Nature (2001) [Pubmed]
  9. Telomeric reciprocal recombination as a possible mechanism for antigenic variation in trypanosomes. Pays, E., Guyaux, M., Aerts, D., Van Meirvenne, N., Steinert, M. Nature (1985) [Pubmed]
  10. Different antiviral spectra of human macrophage interferon activities. Bell, D.M., Roberts, N.J., Hall, C.B. Nature (1983) [Pubmed]
  11. Immunochemical characterization of P pili from invasive Escherichia coli. Hanley, J., Salit, I.E., Hofmann, T. Infect. Immun. (1985) [Pubmed]
  12. Variance in fibronectin binding and fnb locus polymorphisms in Staphylococcus aureus: identification of antigenic variation in a fibronectin binding protein adhesin of the epidemic CMRSA-1 strain of methicillin-resistant S. aureus. Rice, K., Huesca, M., Vaz, D., McGavin, M.J. Infect. Immun. (2001) [Pubmed]
  13. Antigenic lipopolysaccharide components of Legionella pneumophila recognized by monoclonal antibodies: possibilities and limitations for division of the species into serogroups. Helbig, J.H., Kurtz, J.B., Pastoris, M.C., Pelaz, C., Lück, P.C. J. Clin. Microbiol. (1997) [Pubmed]
  14. Evaluation of the C6 peptide enzyme-linked immunosorbent assay for individuals vaccinated with the recombinant OspA vaccine. Marques, A.R., Martin, D.S., Philipp, M.T. J. Clin. Microbiol. (2002) [Pubmed]
  15. Multiple inverted DNA repeats of Bacteroides fragilis that control polysaccharide antigenic variation are similar to the hin region inverted repeats of Salmonella typhimurium. Patrick, S., Parkhill, J., McCoy, L.J., Lennard, N., Larkin, M.J., Collins, M., Sczaniecka, M., Blakely, G. Microbiology (Reading, Engl.) (2003) [Pubmed]
  16. Frequent ectopic recombination of virulence factor genes in telomeric chromosome clusters of P. falciparum. Freitas-Junior, L.H., Bottius, E., Pirrit, L.A., Deitsch, K.W., Scheidig, C., Guinet, F., Nehrbass, U., Wellems, T.E., Scherf, A. Nature (2000) [Pubmed]
  17. Chromosomes of kinetoplastida. Van der Ploeg, L.H., Cornelissen, A.W., Barry, J.D., Borst, P. EMBO J. (1984) [Pubmed]
  18. The var genes of Plasmodium falciparum are located in the subtelomeric region of most chromosomes. Rubio, J.P., Thompson, J.K., Cowman, A.F. EMBO J. (1996) [Pubmed]
  19. Genetic controls for the expression of surface antigens in African trypanosomes. Pays, E., Vanhamme, L., Berberof, M. Annu. Rev. Microbiol. (1994) [Pubmed]
  20. Complete genome sequencing of Anaplasma marginale reveals that the surface is skewed to two superfamilies of outer membrane proteins. Brayton, K.A., Kappmeyer, L.S., Herndon, D.R., Dark, M.J., Tibbals, D.L., Palmer, G.H., McGuire, T.C., Knowles, D.P. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  21. Mutation of human immunodeficiency virus type 1 at amino acid 585 on gp41 results in loss of killing by CD8+ A24-restricted cytotoxic T lymphocytes. Dai, L.C., West, K., Littaua, R., Takahashi, K., Ennis, F.A. J. Virol. (1992) [Pubmed]
  22. The mature erythrocyte surface antigen of Plasmodium falciparum is not required for knobs or cytoadherence. Petersen, C., Nelson, R., Magowan, C., Wollish, W., Jensen, J., Leech, J. Mol. Biochem. Parasitol. (1989) [Pubmed]
  23. In vivo and in vitro effect of cyclophosphamide on Borrelia duttoni. Wright, D.J. Acta Trop. (1979) [Pubmed]
  24. Dynamics of tumor cell killing by human T lymphocytes armed with an anti-carcinoembryonic antigen chimeric immunoglobulin T-cell receptor. Beecham, E.J., Ortiz-Pujols, S., Junghans, R.P. J. Immunother. (2000) [Pubmed]
  25. Isolation of influenzavirus A and B in PLC/PRF/5 cells. Bryden, A.S. Br. J. Biomed. Sci. (1996) [Pubmed]
  26. Antigenic variation of a cysteine-rich protein in Giardia lamblia. Adam, R.D., Aggarwal, A., Lal, A.A., de La Cruz, V.F., McCutchan, T., Nash, T.E. J. Exp. Med. (1988) [Pubmed]
  27. Chemical and serological investigations on the genus-specific lipopolysaccharide epitope of Chlamydia. Brade, H., Brade, L., Nano, F.E. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  28. Characterization of a de novo conversion in human complement C4 gene producing a C4B5-like protein. Jaatinen, T., Eholuoto, M., Laitinen, T., Lokki, M.L. J. Immunol. (2002) [Pubmed]
  29. Functional analysis of matrix proteins expressed from cloned genes of measles virus variants that cause subacute sclerosing panencephalitis reveals a common defect in nucleocapsid binding. Hirano, A., Ayata, M., Wang, A.H., Wong, T.C. J. Virol. (1993) [Pubmed]
  30. Rapid selection of genetic and antigenic variants of foot-and-mouth disease virus during persistence in cattle. Gebauer, F., de la Torre, J.C., Gomes, I., Mateu, M.G., Barahona, H., Tiraboschi, B., Bergmann, I., de Mello, P.A., Domingo, E. J. Virol. (1988) [Pubmed]
  31. A two-locus gene conversion model with selection and its application to the human RHCE and RHD genes. Innan, H. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  32. A homologue of the recombination-dependent growth gene, rdgC, is involved in gonococcal pilin antigenic variation. Mehr, I.J., Long, C.D., Serkin, C.D., Seifert, H.S. Genetics (2000) [Pubmed]
  33. Carcinoembryonic antigen: evidence for multiple antigenic determinants and isoantigens. Vrba, R., Alpert, E., Isselbacher, K.J. Proc. Natl. Acad. Sci. U.S.A. (1975) [Pubmed]
  34. Outer membrane proteins P1 and P2 of Haemophilus influenzae type b: structure and identification of surface-exposed epitopes. Munson, R., Brodeur, B., Chong, P., Grass, S., Martin, D., Proulx, C. J. Infect. Dis. (1992) [Pubmed]
  35. Lack of sequence diversity in the gene encoding merozoite surface protein 5 of Plasmodium falciparum. Wu, T., Black, C.G., Wang, L., Hibbs, A.R., Coppel, R.L. Mol. Biochem. Parasitol. (1999) [Pubmed]
  36. Comparison of two aquatic alphaviruses, salmon pancreas disease virus and sleeping disease virus, by using genome sequence analysis, monoclonal reactivity, and cross-infection. Weston, J., Villoing, S., Brémont, M., Castric, J., Pfeffer, M., Jewhurst, V., McLoughlin, M., Rødseth, O., Christie, K.E., Koumans, J., Todd, D. J. Virol. (2002) [Pubmed]
  37. Interaction of African trypanosomes with the immune system. Askonas, B.A., Bancroft, G.J. Philos. Trans. R. Soc. Lond., B, Biol. Sci. (1984) [Pubmed]
  38. Cell surface antigens of chemically induced sarcomas of murine origin. DeLeo, A.B., Srivastava, P.K. Cancer Surv. (1985) [Pubmed]
  39. Antigenic characteristics of polypeptides of Coxiella burnetii isolates. To, H., Hotta, A., Zhang, G.Q., Nguyen, S.V., Ogawa, M., Yamaguchi, T., Fukushi, H., Amano, K., Hirai, K. Microbiol. Immunol. (1998) [Pubmed]
  40. A serological and biochemical study of new field isolates of foot-and-mouth disease virus type A in Peru, 1975 to 1981. Espinoza, A.M., Knowles, N.J. Vet. Microbiol. (1983) [Pubmed]
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