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Structural correlates of mouse IgA allotypes

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Abstract

A set of mouse IgAs containing amino acids differing amongst the six α-chain allotypes was constructed by mutating an S107-IgA plasmid and transfecting it into a non-producer myeloma cell line along with a κ-chain plasmid. The secreted IgAs were examined for their possession of a covalent bond between α- and light (l)-chains and for their ability to bind to three anti-allotypic monoclonal antibodies, HIS-M2, HY-15, and HY-16. IgA of the Igh-2 a allotype was found to be unique in its total lack of a covalent bond between α and l-chains, formation of which apparently depends on the presence of an “extra” Cys in the hinges of all of the other five allotypes. The allotypic epitopes are associated with identifiable amino acids in the Cα1 region of the molecule. Binding to HIS-M2 requires Ala 216 whereas binding to HY-15 requires Pro 216 and Asp 222. Binding to Hy-16 requires Arg 183 and either Pro 216 or Ser 216 but not Ala 216. However, binding to HY-16 by all of the IgAs produced by transfectants is impaired by defective glycosylation in the transfected myeloma and is only revealed after deglycosylation.

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References

  • Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2008) Molecular biology of the cell, 5th edn. Garland Science, Taylor & Francis Group, New York

    Google Scholar 

  • Arakawa H (1994) Mouse gene for immunoglobulin alpha heavy chain, switch region and constant region complete sequence. Genbank MUSIALPHA. Accession No D11468

  • Auffray C, Nageotte R, Sikorav J-L, Heidmann O, Rougeon F (1981) Mouse immunoglobulin A: nucleotide sequence of the structural gene for the α heavy chain derived from cloned cDNAs. Gene 13:365–374

    Article  CAS  PubMed  Google Scholar 

  • Bevan MJ (1971) Interchain disulfide bond formation studied in two mouse myelomas which secrete immunoglobulin A. Eur J Immunol 1:133–138

    Article  CAS  PubMed  Google Scholar 

  • Chintalacharuvu SR, Emancipator SN (1997) The glycosylation of IgA produced by murine B cells is altered by Th2 cytokines. J Immunol 159:2327–2333

    CAS  PubMed  Google Scholar 

  • Chintalacharuvu SR, Emancipator SN (2000) Differential glycosylation of two glycoproteins synthesized by murine B cells in response to IL-4 plus IL-5. Cytokine 12:1182–1188

    Article  CAS  PubMed  Google Scholar 

  • Chintalacharuvu KR, Morrison SL (1996) Residues critical for HL-disulphide bond formation in human IgA1 and IgA2. J Immunol 157:3443–3449

    CAS  PubMed  Google Scholar 

  • Chintalacharuvu KR, Lamm ME, Kaetzel CS (1993) Unstable inter-H chain disulphide bonding and non-covalently associated J chain in rat dimeric IgA. Mol Immunol 30:19–26

    Article  CAS  PubMed  Google Scholar 

  • Chintalacharuvu KR, Yu J, Bhola N, Kobayashi K, Fernandez CZ, Morrison SL (2002) Cysteine residues required for the attachment of the light chain in human IgA2. J Immunol 169:5072–5077

    PubMed  Google Scholar 

  • Chintalacharuvu SR, Yamashita M, Bagheri N, Blanchard TG, Nedrud JG, Lamm ME, Tomino Y, Emancipator SN (2008) T cell cytokine polarity as a determinant of immunoglobulin A (IgA) glycosylation and the severity of experimental IgA nephropathy. Clin Exp Immunol 153:456–462

    Article  CAS  PubMed  Google Scholar 

  • George J, Penner SJ, Weber J, Berry J, Claflin JL (1993) Influence of membrane Ig receptor density and affinity on B cell signaling by antigen. J Immunol 151:5955–5967

    CAS  PubMed  Google Scholar 

  • Herzenberg LA, Herzenberg LA (1978) Mouse immunoglobulin allotypes: description and special methodology. In: Weir DM (ed) Handbook of experimental immunology, 3rd edn. Blackwell, Oxford, pp 12.1–12.23

    Google Scholar 

  • Kabat EA, Wu TT, Perry AM, Gottesman KS, Foeller C (1991) Sequences of proteins of immunological interest, 5th edn. US Public Health Service, Washington, D.C.

  • Kearney JF, Radbruch A, Liesegang B, Rajewsky K (1979) A new mouse myeloma cell line that has lost immunoglobulin expression but permits the construction of antibody-secreting hybrid cell lines. J Immunol 123:1548–1550

    CAS  PubMed  Google Scholar 

  • Klein J, Herzenberg LA (1967) Congenic mouse strains with different immunoglobulin allotypes. (1) Breeding scheme, histocompatibility tests and genetics of γG2a-globulin production by transferred cells for C3H.SW and its congenic partner CWB/5. Transplantation 5:1484–1495

    Article  CAS  PubMed  Google Scholar 

  • Kroese FGM, Cebra JJ, van der Cammen MJF, Kantor AB, Bos NA (1995) Contribution of B-1 cells to intestinal IgA production in the mouse. Methods 8:37–43

    Article  CAS  Google Scholar 

  • Kyte J (1995) Structure in protein chemistry. Garland Publishing, Inc, New York

    Google Scholar 

  • Lieberman R (1978) Genetics of IgCH (allotype) locus in the mouse. Springer Semin Immunopathol 1:7–30

    Article  Google Scholar 

  • Mestecky J, Moro I, Underdown BJ (1999) Mucosal immunoglobulins. In: Ogra PL, Mestecky J, Lamm ME, Strober W, Bienenstock J, McGhee JR (eds) Mucosal immunology, 2nd edn. Academic Press, New York

    Google Scholar 

  • Parsons M, Oi VT, Huang C-M, Herzenberg LA (1983) Structural characterization of mouse immunoglobulin allotypic determinants defined by monoclonal antibodies. Immunogenetics 18:323–334

    Article  CAS  PubMed  Google Scholar 

  • Petsko GA, Ringe D (2004) Protein structure and function. New Science Press Ltd., London

    Google Scholar 

  • Phillips-Quagliata JM (2002) Mouse IgA allotypes have major differences in their hinge regions. Immunogenetics 53:1033–1038

    Article  CAS  PubMed  Google Scholar 

  • Potter M, Lieberman R (1967) Genetics of immunoglobulins in the mouse. Adv Immunol 7:91–145

    Article  CAS  PubMed  Google Scholar 

  • Randall TD, Parkhouse RM, Corley RB (1992) J chain synthesis and secretion of hexameric IgM is differentially regulated by lipopolysaccharide and interleukin 5. Proc Natl Acad Sci U S A 89:962–966

    Article  CAS  PubMed  Google Scholar 

  • Shulman M, Wilde CD, Kohler G (1978) A better cell line for making hybridomas secreting specific antibodies. Nature 276:269–270

    Article  CAS  PubMed  Google Scholar 

  • Snapper CM, Finkelman FD (1999) Immunoglobulin class switching. In: Paul WE (ed) Fundamental immunology, 4th edn. Lippincott-Raven, Philadelphia, pp 831–861

    Google Scholar 

  • Staats J (1976) Standardized nomenclature for inbred strains of mice: sixth listing. Cancer Res 36:837–839

    Google Scholar 

  • Stall AM (1996) Mouse immunoglobulin allotypes. In: Weir DM (ed) Handbook of experimental immunology, 5th edn. Blackwell, Oxford, pp 27.1–27.16

    Google Scholar 

  • Stanitz AM, Lieberman R, Kaplan A, Davie JM (1983) IgA polymorphism in mice: NZB and BALB/c mice produce two forms of IgA. Mol Immunol 20:983–988

    Article  Google Scholar 

  • Stavnezer J, Kang J (2009) The surprising discovery that TGFβ specifically induces the IgA class switch. J Immunol 182:5–7

    CAS  PubMed  Google Scholar 

  • Tada N, Kimura S, Binari R, Liu Y, Hammerling U (1981) New mouse immunoglobulin A heavy chain allotype specificities detected using the hybridoma-derived IgA of I/St mice. Immunogenetics 13:475–481

    Article  CAS  PubMed  Google Scholar 

  • Tsuzukida T, Wang C-C, Putnam FW (1979) Structure of the A2m(1) allotype of human IgA—a recombinant molecule. Proc Natl Acad Sci USA 76:1104–1108

    Article  CAS  PubMed  Google Scholar 

  • Tucker PW, Slightom JL, Blattner FR (1981) Mouse IgA heavy chain gene sequence: implications for evolution of immunoglobulin hinge exons. Proc Natl Acad Sci USA 78:7684–7688

    Article  CAS  PubMed  Google Scholar 

  • Warner NL, Marchalonis JJ (1972) Structural differences in mouse IgA myeloma proteins of different allotypes. J Immunol 109:657–661

    CAS  PubMed  Google Scholar 

  • Wims LA, Sharon J, Newman B, Kabat EA, Morrison SL (1985) C57BL/6 X BALB/c hybridomas produce IgA which assembles into molecules with covalent bonds between heavy chains (H) and light chains (L) and into molecules lacking covalent bonds between H and L. Mol Immunol 22:1379–1386

    Article  CAS  PubMed  Google Scholar 

  • Yoo EM, Chintalacharuvu KR, Penichet ML, Morrison SL (2002) Myeloma expression systems. J Immunol Methods 261:1–20

    CAS  PubMed  Google Scholar 

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Acknowledgements

I am most grateful to Dr. Michael E. Lamm for his helpful comments on this paper.

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The author declares no conflict of interest.

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Correspondence to Julia M. Phillips-Quagliata.

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Phillips-Quagliata, J.M. Structural correlates of mouse IgA allotypes. Immunogenetics 62, 1–13 (2010). https://doi.org/10.1007/s00251-009-0414-7

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