Skip to main content
Log in

The thioester and isotypic sites of complement component C4 in sheep and cattle

  • Original Articles
  • Published:
Immunogenetics Aims and scope Submit manuscript

Abstract

The region inclusive of the thioester and the isotype-determining sites of the sheep C4 genes from a single animal was amplified by polymerase chain reaction (PCR). Two bands, at 880 base pairs (bp) and 1000 bp, were resolved by agarose gel electrophoresis. Four different clones were obtained for the 880 bp (type 1) product and two from the 1000 bp (type 2) product. Two of the type 1 clones (type 1H) and both type 2 clones (type 2H) code for the PCPVIH sequence at the isotypic site whereas the other two type 1 clones (type 1D) code for the PFPVMD sequence. By restriction mapping and Southern blot analysis, there appears to be four C4 gene loci for the sheep: two type 1H, one type 1D, and one type 2H. The type 1H and type 2H genes are likely to code for proteins with C4B-like properties whereas the type 1D genes for proteins with C4A-like properties. The same region of the sheep C4 genes of nine other breeds of sheep are also amplified by PCR and analyzed by restriction mapping and Southern hybridization. Each of the sheep has type 1H, type 2H, and type 1D genes and appears to have four C4 gene loci except for the Orkney, which may have five. A single band of 880 bp was obtained from the PCR product from the genomic DNA of a single cow. Five different clones were identified, two of which code for the PFPVMD sequence and three for the PCPVIH sequence at the isotypic site, which is consistent with previous finding that C4 proteins with A- and B-like activities could be purified from the plasma of the same animal. Comparison of the nucleotide sequences of the isotype-determining region of the sheep and cattle C4 genes with those of the primates and mouse suggests that the C4A-like genes evolved independently in the primates and the ungulates.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Alderson, L.: The Chance to Survive. Helm, Bromley, UK, 1990

    Google Scholar 

  • Belt, K. T., Carroll, M. C., and Porter, R. R.: The structure basis of the multiple forms of human complement component C4. Cell 36: 907–914, 1984

    Article  CAS  PubMed  Google Scholar 

  • Belt, K. T., Yu, C. Y., Carroll, M. C., and Porter, R. R.: Polymorphism of human complement C4. Immunogenetics 21: 173–180, 1985

    Google Scholar 

  • Bitter-Suermann, D., Kroenke, M., Brade, V., and Hadding, U.: Inherited polymorphism of guinea-pig factor B and C4: Evidence for genetic linkage between the Bf and C4 loci. J Immunol 118: 1822–1826, 1977

    Google Scholar 

  • Bontrop, R. E., Broos, L. A. M., Otting, N., and Jonker, M. J.: Polymorphism of C4 and CYP21 genes in various primate species. Tissue Antigens 37: 145–151, 1990

    Google Scholar 

  • Campbell, R. D., Law, S. K. A., Reid, K. B. M., and Sim, R. B.: Structural organization and regulation of the complement genes. Annu Rev Immunol 6: 161–195, 1988

    Google Scholar 

  • Carroll, M. C., Fathallah, D. M., Bergamaschini, L., Alicot, E. M., and Isenman, D. E.: Substitution of a single amino acid (aspartic acid for histidine) converts the functional activity of human complement C4B to C4A. Proc Natl Acad Sci USA 87: 6868–6872, 1990

    Google Scholar 

  • Christiansen, F. T., Bontrop, R. E., Giphart, M., Cameron, P. U., Zhang, W. J., Townend, D., Jonker, M., and Dawkins, R. L.: Major histocompatibility complex ancestral haplotypes in the chimpanzee: identification using C4 allotyping. Hum Immunol 31: 34–39, 1991

    Google Scholar 

  • Collier, S., Simnot, P. J., Dyer, P. A., Price, D. A., Harris, R., and Strachan, T.: Pulsed field electrophoresis identifies a high degree of variability in the number of 21-hydroxylase and complement component C4 gene repeats in 21-hydroxylase deficiency haplotypes. EMBO J 8: 1393–1402, 1989

    Google Scholar 

  • De Kroon, A. I. P. M., Doxiadis, G., Doxiadis, I., and Hensen, E. J.: Structure and polymorphism of the feline complement component C4. Immunogenetics 24: 202–205, 1986

    Google Scholar 

  • Dodds, A. W., Law, S. K. A., and Porter, R. R.: The origin of the very variable haemolytic activities of the common human complement component C4 allotypes including C4A6. EMBO J 4: 2239–2244, 1985

    Google Scholar 

  • Dodds, A. W., Law, S. K. A., and Porter, R. R.: The purification and properties of some less common allotypes of the fourth component of human complement. Immunogenetics 24: 279–285, 1986

    Google Scholar 

  • Dodds, A. W. and Law, S. K. A.: The complement C4 of mammals. Biochem J 265: 495–502, 1990

    Google Scholar 

  • Doxiadis, G., Rebmann, V., Doxiadis, I., Krumbacher, K., Vriesendorp, H. M., and Grosse-Wilde, H.: Polymorphism of the fourth complement component in the dog. Immunobiology 169: 563–569, 1985

    Google Scholar 

  • Ferreira, A., Nussenzweig, V., and Gigli, I.: Structural and functional differences between the H-2 controlled Ss and Slp proteins. J Exp Med 148: 1186–1197, 1978

    Google Scholar 

  • Fielder, A. H., Walport, M. J., Batchelor, J. R., Rynes, R. I., Black, C. M., Dodi, I. A., and Hughes, G. R.: Family study of the major histocompatibility complex in patients with systemic lupus erythematosus: importance of null alleles of C4A and C4B in determining disease susceptibility. Br Med J Clin Res 286: 425–428, 1983

    Google Scholar 

  • Groth, D. M., Wetherall, J. D., Umotong, B. A., Sparrow, P., Lee, I. R., and Carrick, M. J.: Purification and characterisation of the fourth component of bovine complement. Complement Inflamm 4: 1–11, 1987

    Google Scholar 

  • Groth, D. M., Wetherall, J. D., Taylor, L., Sparrow, P. R., and Lee, I. R.: Purification and characterisation of ovine C4: evidence for two molecular forms in ovine plasma. Mol Immunol 25: 577–584, 1988

    Google Scholar 

  • Isenman, D. E. and Young, J. R.: The molecular basis for the difference in immune hemolysis activity of the Chido and Rodgers isotype of human complement component C4. J Immunol 132: 3019–3027, 1984

    Google Scholar 

  • Kawaguchi, H., Golubic, M., Figueroa, F., and Klein, J.: Organisation of the chimpanzee C4-CYP21 region: implications for the evolution of human genes. Eur J Immunol 20: 739–745, 1990

    Google Scholar 

  • Kawaguchi, H., O'hUigin, C., and Klein, J.: Evolution of primate C4 and CYP21 genes. In J. Klein and D. Klein (eds.): Molecular Evolution of the Major Histocompatibility Complex, pp. 357–382, Springer, Heidelberg, 1991

    Google Scholar 

  • Kawaguchi, H., Zaleska-Rutczynska, Z., Figueroa, F., O'hUigin, C., and Klein, J.: C4 Genes of the chimpanzee, gorilla, and orang-utan: Evidence for extensive homogenisation. Immunogenetics 35: 16–23, 1992

    Google Scholar 

  • Kay, P. H. and Dawkins, R. L.: Genetic polymorphism of complement C4 in dog. Tissue Antigens 23: 151–155, 1984

    Google Scholar 

  • Kay, P. H., Dawkins, R. L., Bowling, A. T., and Bernoco, D.: Heterogeneity and linkage of equine C4 and steroid 21-hydroxylase genes. J Immunogenet 14: 247–253, 1987

    Google Scholar 

  • Kirszenbaum, M., Renard, C., Geffrotin, C., Chardon, P., and Vaiman, M.: Evidence for mapping pig C4 gene(s) within the pig major histocompatibility complex (SLA). Anim Blood Groups Biochem Genet 16: 65–68, 1985

    Google Scholar 

  • Law, S. K. A., Dodds, A. W., and Porter, R. R.: A comparison of the properties of the two classes, C4A and C4B, of the human complement component C4. EMBO J 3: 1819–1823, 1984

    Google Scholar 

  • Levi-Strauss, M., Tosi, M., Steinmetz, M., Klein, J., and Meo, T.: Multiple duplications of C4 genes correlate with H-2 controlled testosterone independent expression of its sex-limited isoform, C4-Slp. Proc Natl Acad Sci USA 82: 1746–1750, 1985

    Google Scholar 

  • Mauff, G., Brenden, M., Braun-Stilwell, M., Doxiadis, G., Giles, C. M., Hauptman, G., Rittner, C., Schneider, P. M., Stradmann-Bellinghausen, B., and Uring-Lambert, B.: C4 reference typing report. Complement Inflamm 7: 193–212, 1990

    Google Scholar 

  • Nonaka, M., Nakayama, K., Yeul, Y. D., and Takahashi, M.: Complete nucleotide and derived amino acid sequences of the fourth component of mouse complement (C4). Evolutionary aspects. J Biol Chem 260: 10936–10943, 1985

    Google Scholar 

  • Ogata, R. T. and Sepich, D. S.: Murine sex-limited protein: complete cDNA sequence and comparison with murine fourth complement component. J Immunol 135: 4239–4244, 1985

    Google Scholar 

  • Ogata, R. T., Rosa, P. A., and Zepf, N. E.: Sequence of the gene for murine complement component C4. J Biol Chem 264: 16565–16572, 1989

    Google Scholar 

  • Porter, R. R.: Complement polymorphism, the major histocompatibility complex and associated diseases: a speculation. Mol Biol Med 1: 161–168, 1983

    Google Scholar 

  • Ryder, M. L.: Sheep and Man. Duckworth, London, UK, 1984

    Google Scholar 

  • Sambrook, J., Fritsch, E. F., and Maniatis, T.: Molecular cloning. A Laboratory Manual, 2nd ed. Cold Spring Harbour Press, Cold Spring Harbour, NY, 1989

    Google Scholar 

  • Schifferli, J. A., Hauptmann, G., and Paccaud, J. P.: Complement mediated adherence of immune complexes to human erythrocytes. Difference in the requirements for C4A and C4B. FEBS Lett 213: 415–418, 1987

    Google Scholar 

  • Sepich, D. S., Noonan, D. J., and Ogata, R. T.: Complete cDNA sequence of the fourth component of murine complement. Proc Natl Acad Sci USA 82: 5895–5899, 1985

    Google Scholar 

  • Spilliaert, R., Palsdottir, A., and Arnason, A.: Analysis of the C4 genes in baleen whales using a human cDNA probe. Immunogenetics 32: 73–76, 1990

    Google Scholar 

  • Staden, R.: An interactive graphics programme for comparing and aligning nucleic acid and amino acid sequences. Nucleic Acids Res 10: 2951–2961, 1982

    Google Scholar 

  • Staden, R.: Graphic methods to determine the function of nucleic acid sequences. Nucleic Acids Res 12: 521–538, 1984

    Google Scholar 

  • Tosi, M., Levi-Strauss, M., Georgatsou, E., Amor, M., and Meo, T.: Duplications of complement and non-complement genes of the H-2S region: evolutionary aspects of the C4 isotypes and molecular analysis of their expression variants. Immunol Rev 87:151–183, 1985

    Google Scholar 

  • Yu, C. Y., Belt, K. T., Giles, C. M., Campbell, R. D., and Porter, R. R.: Structural basis of the polymorphism of human complement components C4A and C4B: gene size, reactivity and antigenicity. EMBO J 5: 2873–2881, 1986

    Google Scholar 

  • Yu, C. Y.: The complete exon-intron structure of a human complement component C4 gene: DNA sequences, polymorphism, and linkage to the 21-hydroxylase gene. J Immunol 146: 1057–1066, 1991

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Correspondence to: S. K. A. Law.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ren, XD., Dodds, A.W. & Law, S.K.A. The thioester and isotypic sites of complement component C4 in sheep and cattle. Immunogenetics 37, 120–128 (1993). https://doi.org/10.1007/BF00216835

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00216835

Keywords

Navigation