Biochemistry (Moscow)

, Volume 72, Issue 5, pp 485–494 | Cite as

Unknown functions of immunoglobulins A

  • T. N. Kazeeva
  • A. B. ShevelevEmail author


Traditionally, the function of immunoglobulins A (IgA), the major type of secreted antibodies, has been thought to be restricted to binding antigens outside the epithelium basal membrane. Therefore, effector mechanisms eliminating IgA-opsonized targets have not been investigated so far. However, some indirect observations of infectious agents penetrating into tissues and blood from the environment suggest such mechanisms (analogous to IgG/IgM-dependent activation of complement and natural killers). In the present review, we examine details of IgA structure that might contribute to elucidation of IgA-dependent effector functions in human and animal immunity. Special attention is given to a putative transduction of signal about antigen binding in the active center of IgA from the Fab-to the Fc-superdomain via intramolecular conformational rearrangements. Different structure of the IgA subclasses (IgA1 and IgA2) is examined taking into account probable divergence of their functions in immune response.

Key words

secretory immunity IgA antibodies effectors IgA1-proteases CD89 respiratory burst 



amino acid residue

CHα (Cα)

constant domain of heavy (α) IgA chain


variable antigen-binding superdomain of Ig


constant superdomain of Ig

Fcα R

receptor specific for Fc-superdomain of IgA


component of the heavy chain within Fabα-fragment




5-iodo-4-hydroxy-3-nitrophenylacetyl (hapten)


polymeric immunoglobulin receptor


secretory component of Ig


secreted form of IgA


variable region of Ig


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  1. 1.
    Roitt, I., Brostoff, J., and Male, D. (2000) Immunology [Russian translation], Mir, Moscow.Google Scholar
  2. 2.
    Mestecky, J., and Russell, M. W. (1986) Monogr. Allergy, 19, 277–301.PubMedGoogle Scholar
  3. 3.
    Kerr, M. A. (1990) Biochem. J., 271, 285–296.PubMedGoogle Scholar
  4. 4.
    Woof, J. M., and Mestecky, J. (2005) Immunol. Rev., 206, 64–82.PubMedCrossRefGoogle Scholar
  5. 5.
    Biewenga, J. (1995) Adv. Exp. Med. Biol., 371A, 575–579.PubMedGoogle Scholar
  6. 6.
    Sumiyama, K., Saitou, N., and Ueda, Sh. (2002) Mol. Biol. Evol., 19, 1093–1099.PubMedGoogle Scholar
  7. 7.
    Chintalacharuvu, K. R., Raines, M., and Morrison, S. L. (1994) J. Immunol., 152, 5299–5304.PubMedGoogle Scholar
  8. 8.
    Almogren, A., Senior, B., Loomes, L., and Kerr, M. (2003) Infect. Immun., 71, 3349–3356.PubMedCrossRefGoogle Scholar
  9. 9.
    Chintalacharuvu, K. R., Yu, L. J., Bhola, N., Kobayashi, K., Fernandez, C. Z., and Morrison, S. L. (2002) J. Immunol., 169, 5072–5077.PubMedGoogle Scholar
  10. 10.
    Bertrand, F. E., Billips, L. G., Gartland, G. L., Kubagawa, H., and Schroeder, H. W. (1996) J. Immunol., 156, 4240–4244.PubMedGoogle Scholar
  11. 11.
    Atkin, J. D., Pleass, R. J., Owens, R. J., and Woof, J. M. (1996) J. Immunol., 157, 156–159.PubMedGoogle Scholar
  12. 12.
    Krugmann, S., Pleass, R. J., Atkin, J. D., and Woof, J. M. (1997) Biochem. Soc. Trans., 25, 323S.PubMedGoogle Scholar
  13. 13.
    Braathen, R., Sorensen, V., Brandtzaeg, P., Sandlie, I., and Johansen, F. (2002) J. Biol. Chem., 277, 42755–42762.PubMedCrossRefGoogle Scholar
  14. 14.
    Krugmann, S., Pleass, R. J., Atkin, J. D., and Woof, J. M. (1997) J. Immunol., 159, 244–249.PubMedGoogle Scholar
  15. 15.
    Mestecky, J., Russell, M. W., Jackson, S., and Brown, T. A. (1986) Clin. Immunol. Immunopathol., 40, 105–114.PubMedCrossRefGoogle Scholar
  16. 16.
    Woof, J. M., and Kerr, M. A. (2006) J. Pathol. 208, 270–282.PubMedCrossRefGoogle Scholar
  17. 17.
    Snoeck, V., Peters, I. R., and Cox, E. (2006) Vet. Res., 37, 455–467.PubMedCrossRefGoogle Scholar
  18. 18.
    Perrier, C., Sprenger, N., and Corthesy, B. (2006) J. Biol. Chem., 281, 14280–14287.PubMedCrossRefGoogle Scholar
  19. 19.
    Strong, R. K. (2004) Structure, 12, 1919–1920.PubMedCrossRefGoogle Scholar
  20. 20.
    Chang, Y., Lee, T. C., Li, J. C., Lai, T. L., Chua, H. H., Chen, C. L., Doong, S. L., Chou, C. K., Sheen, T. S., and Tsai, C. H. (2005) Head Neck., 27, 873–882.PubMedCrossRefGoogle Scholar
  21. 21.
    Johansen, F. E., Braathen, R., and Brandtzaeg, P. (2001) J. Immunol., 167, 5185–5192.PubMedGoogle Scholar
  22. 22.
    Kaetzel, C. S. (2005) Immunol. Rev., 206, 83–99.PubMedCrossRefGoogle Scholar
  23. 23.
    Braathen, R., Sandvik, A., Berntzen, G., Hammerschmidt, S., Fleckenstein, B., Sandlie, I., Brandtzaeg, P., Johansen, F. E., and Lauvrak, V. (2006) J. Biol. Chem., 281, 7075–7081.PubMedCrossRefGoogle Scholar
  24. 24.
    Lewis, M. J., Pleass, R. J., Batten, M. R., Atkin, J. D., and Woof, J. M. (2005) J. Immunol., 175, 6694–6701.PubMedGoogle Scholar
  25. 25.
    Brandtzaeg, P., and Johansen, F. E. (2001) Trends Immunol., 22, 545–546.PubMedCrossRefGoogle Scholar
  26. 26.
    Hamburger, A. E., West, A. P., Jr., and Bjorkman, P. J. (2004) Structure, 12, 1925–1935.PubMedCrossRefGoogle Scholar
  27. 27.
    Brandtzaeg, P., and Johansen, F. E. (2005) Immunol. Rev., 206, 32–63.PubMedCrossRefGoogle Scholar
  28. 28.
    Mestecky, J., Lue, C., and Russell, M. W. (1991) Gastroenterol. Clin. North. Am., 20, 441–471.PubMedGoogle Scholar
  29. 29.
    Tarkowski, A., Moldoveanu, Z., Koopman, W. J., Radl, J., Haaijman, J. J., and Mestecky, J. (1991) Clin. Exp. Immunol., 85, 341–348.PubMedCrossRefGoogle Scholar
  30. 30.
    Mestecky, J., Moldoveanu, Z., Prince, S. J., Kutteh, W. H., Kulhavy, R., McGhee, J. R., Moro, I., and Crago, S. S. (1991) Adv. Exp. Med. Biol., 310, 123–129.PubMedGoogle Scholar
  31. 31.
    McGhee, J. R., Fujihashi, K., Lue, C., Beagley, K. W., Mestecky, J., and Kiyono, H. (1991) Adv. Exp. Med. Biol., 310, 113–121.PubMedGoogle Scholar
  32. 32.
    Plaut, A. (1983) Ann. Rev. Microbiol., 37, 603–622.CrossRefGoogle Scholar
  33. 33.
    Mistry, D., and Stockley, R. A. (2006) Int. J. Biochem. Cell. Biol., 38, 1244–1248.PubMedCrossRefGoogle Scholar
  34. 34.
    Gilbert, J. V., Plaut, A. G., and Wright, A. (1991) Infect. Immun., 59, 7–10.PubMedGoogle Scholar
  35. 35.
    Mulks, M. H., Plaut, A. G., Feldman, H. A., and Frangione, B. (1980) J. Exp. Med., 152, 1442–1447.PubMedCrossRefGoogle Scholar
  36. 36.
    Plaut, A. G. (1988) Meth. Enzymol., 165, 117–120.PubMedCrossRefGoogle Scholar
  37. 37.
    Kirkeby, L., Rasmussen, T. T., Reinholdt, J., and Kilian, M. (2000) Clin. Diagn. Lab. Immunol., 7, 31–39.PubMedGoogle Scholar
  38. 38.
    Mansa, B., and Kilian, M. (1986) Infect. Immun., 52, 171–174.PubMedGoogle Scholar
  39. 39.
    Monteiro, R. C., and van de Winkel, J. G. (2003) Ann. Rev. Immunol., 21, 177–204.CrossRefGoogle Scholar
  40. 40.
    Morton, H. C., and Brandtzaeg, P. (2001) Arch. Immunol. Ther. Exp. (Warsz), 49, 217–229.Google Scholar
  41. 41.
    Yan, H., Lamm, M. E., Bjorling, E., and Huang, Y. T. (2002) J. Virol., 76, 10972–10979.PubMedCrossRefGoogle Scholar
  42. 42.
    Asahi-Ozaki, Y., Yoshikawa, T., Iwakura, Y., Suzuki, Y., Tamura, S., Kurata, T., and Sata, T. (2004) J. Med. Virol., 74, 328–335.PubMedCrossRefGoogle Scholar
  43. 43.
    Pal, K., Kaetzel, C. S., Brundage, K., Cunningham, C. A., and Cuff, C. F. (2005) J. Gen. Virol., 86, 2347–2357.PubMedCrossRefGoogle Scholar
  44. 44.
    Schneeman, T. A., Bruno, M. E., Schjerven, H., Johansen, F. E., Chady, L., and Kaetzel, C. S. (2005) J. Immunol., 175, 376–384.PubMedGoogle Scholar
  45. 45.
    Dotzauer, A., Brenner, M., Gebhardt, U., and Vallbracht, A. (2005) J. Gen. Virol., 86, 2747–2751.PubMedCrossRefGoogle Scholar
  46. 46.
    Russell, M. W., Reinholdt, J., and Kilian, M. (1989) Eur. J. Immunol., 19, 2243–2249.PubMedCrossRefGoogle Scholar
  47. 47.
    Jarvis, G. A., and Griffiss, J. M. (1989) J. Immunol., 143, 1703–1709.PubMedGoogle Scholar
  48. 48.
    Van Spriel, A. B., and van de Winkel, J. G. (2001) J. Biol. Regul. Homeost. Agents, 15, 179–181.PubMedGoogle Scholar
  49. 49.
    Mazanec, M. B., Coudret, C. L., and Fletcher, D. R. (1995) J. Virol., 69, 1339–1343.PubMedGoogle Scholar
  50. 50.
    Bomsel, M., Heyman, M., Hocini, H., Lagaye, S., Belec, L., Dupont, C., and Desgranges, C. (1998) Immunity, 9, 277–287.PubMedCrossRefGoogle Scholar
  51. 51.
    Mazengera, R. L., and Kerr, M. A. (1990) Biochem. J., 272, 159–165.PubMedGoogle Scholar
  52. 52.
    Morton, H. C., Pleass, R. J., Woof, J. M., and Brandtzaeg, P. (2004) J. Biol. Chem., 279, 54018–54022.PubMedCrossRefGoogle Scholar
  53. 53.
    Morton, H. C., Pleass, R. J., Storset, A. K., Brandtzaeg, P., and Woof, J. M. (2005) Immunology, 115, 74–84.PubMedCrossRefGoogle Scholar
  54. 54.
    Morton, H. C., Pleass, R. J., Storset, A. K., Dissen, E., Williams, J. L., Brandtzaeg, P., and Woof, J. M. (2004) Immunology, 111, 204–211.PubMedCrossRefGoogle Scholar
  55. 55.
    Pleass, R. J., Dunlop, J. I., and Woof, J. M. (1997) Biochem. Soc. Trans., 25, 327S.PubMedGoogle Scholar
  56. 56.
    Herr, A. B., Ballister, E. R., and Bjorkman, P. J. (2003) Nature, 338, 921–941.Google Scholar
  57. 57.
    Pleass, R. J., Dehal, P. K., Lewis, M. J., and Woof, J. M. (2003) Immunology, 109, 331–335.PubMedCrossRefGoogle Scholar
  58. 58.
    Pleass, R. J., Dunlop, J. I., Anderson, C. M., and Woof, J. M. (1999) J. Biol. Chem., 274, 23508–23514.PubMedCrossRefGoogle Scholar
  59. 59.
    Mattu, T. S., Pleass, R. J., Willis, A. C., Kilian, M., Wormald, M. R., Lellouch, A. C., Rudd, P. M., Woof, J. M., and Dwek, R. A. (1998) J. Biol. Chem., 273, 2260–2272.PubMedCrossRefGoogle Scholar
  60. 60.
    Pleass, R. J., Anderson, C. M., Dunlop, J. I., and Woof, J. M. (1997) Biochem. Soc. Trans., 25, 328S.PubMedGoogle Scholar
  61. 61.
    Pleass, R. J., Areschoug, T., Lindahl, G., and Woof, J. M. (2001) J. Biol. Chem., 276, 8197–8204.PubMedCrossRefGoogle Scholar
  62. 62.
    Podbielski, A., Schnitzler, N., Beyhs, P., and Boyle, M. D. (1996) Mol. Microbiol., 19, 429–441.PubMedCrossRefGoogle Scholar
  63. 63.
    Boehm, M. K., Woof, J. M., Kerr, M. A., and Perkins, S. J. (1999) J. Mol. Biol., 286, 1421–1447.PubMedCrossRefGoogle Scholar
  64. 64.
    Woof, J. M. (2002) Biochem. Soc., 30, 491–494.CrossRefGoogle Scholar
  65. 65.
    Zhang, W., Voice, J., and Lachmann, P. J. (1995) Clin. Exp. Immunol., 101, 507–514.PubMedCrossRefGoogle Scholar
  66. 66.
    Johnsson, E., Areschoug, T., Mestecky, J., and Lindahl, G. (1999) J. Biol. Chem., 274, 14521–14524.PubMedCrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2007

Authors and Affiliations

  1. 1.Bach Institute of BiochemistryRussian Academy of SciencesMoscowRussia

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