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Antibodies (Ab), especially natural, display multiple specificity not only due to intrinsic conformational dynamics. With computational analysis the distribution of identical and homologous peptides has been studied in surface proteins from RNA and DNA viruses of widely distributed infections. It was established that each virus protein shared the fragments homologous to other virus proteins that allowed to propose the existence of the peptide continuum of the protein relationship (PCPR). Possible manifestations of PCPR are multiple reactivity and autoreactivity in Ab and therefore it is not possible to consider the immune methods of virus identification as high reliable because of crossing interactions. The PCPR excludes the existence of 100% specificity in immune tests for virus identification. Immunodiagnostic collisions may occur either in identification of virus itself or identification of Ab to viruses. Also PCPR may be responsible for heterologous immunity and consequently the infection associated with severe pathology. The comparative analysis of peptide relationship of H1N1 influenza virus nucleoprotein and human proteins found out, beyond early described its common motif with human hypocretin receptor 2, peptides homologous to those in melanotonin and glutamate receptors and three ion channels. It allows to propose that the sleep disorder narcolepsy associated with Pandemrix vaccination (an adjuvanted, influenza pandemic vaccine) and also with infection by influenza virus during the 2009 A(H1N1) influenza pandemic may be determined not only by Ab to the peptide motif common to influenza nucleoprotein and hypocretin receptor but also Ab to melanotonin and glutamate receptors and ion channels. Decreasing and even avoiding risks of complications from vaccination may be feasible by means of a computer analysis of vaccine proteins for the occurrence of epitopes homologous to the human protein those and particularly by an analysis of Ab profiles induced by vaccine using microarrays with the large number of human protein antigens.

About the authors

E. P. Kharchenko

Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences

Author for correspondence.
194223, St. Petersburg, Toreza pr., 44 Russian Federation


  1. Харченко Е.П. Иммуноэпитопный континуум родства белков и полиреактивность и аутореактивность антител // Медицинская иммунология. 2015. Т. 17, № 4. C. 335–346 [Kharchenko E.P. Immune Epitope continuum of the protein relationships, poly- and autoreactivity of antibodies] Meditsinskaya Immunologiya = Medical Immunology (Russia), 2015, vol. 17, no. 4, pp. 335–346. doi: 10.15789/1563-0625-2015-4-335-346 (In Russ.)]
  2. Харченко Е.П. Эволюционные аспекты оценки возможного числа и источников белковых регуляторов в организме // Журнал эволюционной биохимии и физиологии. 1988. Т. 24. С. 240–249. [Kharchenko E.P. Evolutionary aspects of evaluation of possible number and sources of protein regulators in the organism. Zhurnal evolyutsionnoi biokhimii i fiziologii = Journal of Evolutionary Biochemistry and Physiology, 1989, vol. 25, no. 2, pp. 176–181. (In Russ.)]
  3. Ahmed S.S., Volkmuth W., Duca J., Corti L., Pallaoro M., Pezzicoli A., Karle A., Rigat F., Rappuoli R., Narasimhan V., Julkunen I., Vuorela A., Vaarala O., Nohynek H., Pasini F.L., Montomoli E., Trombetta C., Adams C.M., Rothbard J., Steinman L., Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2. Sci. Transl. Med., 2015, vol. 7, no. 294:ra105. doi: 10.1126/scitranslmed.aab2354
  4. Gil A., Kenney L.L., Mishra R., Watkin L.B., Aslan N., Selin L.K. Vaccination and heterologous immunity: educating the immune system. Trans. R. Soc. Trop. Med. Hyg., 2015, vol. 109, no. 1, pp. 62–69. doi: 10.1093/trstmh/tru198
  5. Gunti S., Messer R.J., Xu C., Yan M., Coleman W.G., Peterson K.E., Hasenkrug K.J., Notkins A.L. Stimulation of Toll-like receptors profoundly influences the titer of polyreactive antibodies in the circulation. Sci. Rep., 2015, vol. 5:15066. doi: 10.1038/srep15066
  6. Haynes B.F., Moody M.A., Alam M., Bonsignori M., Verkoczy L., Ferrari G., Gao F., Tomaras G.D., Liao H.X., Kelsoe G. Progress in HIV-1 vaccine development. J. Allergy Clin. Immunol., 2014, vol. 134, pp. 3–10. doi: 10.1016/j.jaci.2014.04.025
  7. Nagele E.P., Han M., Acharya N.K., DeMarshall C., Kosciuk M.C., Nagele R.G. Natural IgG autoantibodies are abundant and ubiquitous in human sera, and their number is influenced by age, gender, and disease. PLoS ONE, 2013, vol. 8, no. 4:e60726. doi: 10.1371/journal.pone.0060726
  8. Poropatich K., Sullivan D.J. Jr. Human immunodeficiency virus type I long-term non-progressors: the viral genetic and immunological basis for disease non-proeression II. J. Gen. Virol., 2011, vol. 92, pt. 2, pp. 247– 268. doi: 10.1099/vir.0.027102-0
  9. Rothstein T.L., Griffin D.O., Holodick N.E., Quach T.D., Kaku H. Human B-1 cells take the stage. Ann. NY Acad. Sci., 2013, vol. 1285, pp. 97–114. doi: 10.1111/nyas.12137
  10. Selin L.K., Wlodarczyk M.F., Kraft A.R., Nie S., Kenney L.L., Puzone R., Celada F. Heterologous immunity: immunopathology, autoimmunity and protection during viral infections. Autoimmunity, 2011, vol. 44, pp. 328–347. doi: 10.3109/08916934.2011.523277
  11. Sharma S., Thomas P.G. The two faces of heterologous immunity: protection or immunopathology. J. Leukoc. Biol., 2014, vol. 95, pp. 405–416. doi: 10.1189/jlb.0713386
  12. Shen Z.T., Nguyen T.T., Daniels K.A., Welsh R.M., Stern L.J. Disparate epitopes mediating protective heterologous immunity to unrelated viruses share peptide-MHC structural features recognized by cross-reactive T cells. J. Immunol., 2013, vol. 191, no. 10, pp. 5139–5152. doi: 10.4049/jimmunol.1300852
  13. Van Regenmortel M. An outdated notion of antibody specificity is one of the major detrimental assumptions of the structurebased reverse vaccinology paradigm, which prevented it from helping to develop an effective HIV-1 vaccine. Front Immunol., 2014, vol. 5:593. doi: 10.3389/fimmu.2014.00593
  14. Verkoczy L., Diaz M., Holl T.M., Ouyang Y.B., Bouton-Verville H., Alam S.M., Liao H.X., Kelsoe G., Haynes B.F. Autoreactivity in an HIV-1 broadly reactive neutralizing antibody variable region heavy chain induces immunologic tolerance. Proc. Natl. Acad. Sci. USA, 2010, vol. 107, pp. 181–186. doi: 10.1073/pnas.0912914107
  15. Vujicić A.D., Gemović B., Veljković V., Glisić S., Veljković N. Natural autoantibodies in healthy neonatals recognizing a peptide derived from the second conserved region of HIV-1 gp120. Vojnosanit Pregl., 2014, vol. 71, no. 4, pp. 352–361.
  16. Welsh R.M., Che J.W., Brehm M.A., Selin L.K. Heterologous immunity between viruses. Immunol. Rev., 2010, vol. 235, no. 1, pp. 244–266. doi: 10.1111/j.0105-2896.2010.00897.x
  17. Yang G., Holl T.M., Liu Y, Li Y., Lu X., Nicely N.I., Kepler T.B., Alam S.M., Liao H.X., Cain D.W., Spicer L., VandeBerg J.L., Haynes B.F., Kelsoe G. Identification of autoantigens recognized by the 2F5 and 4e10 broadly neutralizing HIV-1 antibodies. J. Exp. Med., 2013, vol. 210, no. 2, pp. 241–256. doi: 10.1084/jem.20121977

Copyright (c) 2016 Kharchenko E.P.

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