Skip to main content
Immunology logoLink to Immunology
. 1985 Jun;55(2):185–196.

Application of molecular cloning to studies on the complement system.

K B Reid
PMCID: PMC1453608  PMID: 3159649

Abstract

The isolation of cDNA and, in certain cases, genomic clones has been reported for the following complement proteins: C1q, C2, C3, C4, C5, C9, and factor B, C4b-binding protein and C1-inhibitor. The availability of cloned DNA has allowed rapid advances to be made in the understanding of the structure (from the derived amino acid sequences), function, biosynthesis and genetics of these proteins. This is most strongly illustrated from recent studies on the C2, factor B and C4 genes, which code for the class III molecules of the major histocompatibility complex, especially as certain allelic forms of these genes may be associated with disease susceptibility.

Full text

PDF
189

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Belt K. T., Carroll M. C., Porter R. R. The structural basis of the multiple forms of human complement component C4. Cell. 1984 Apr;36(4):907–914. doi: 10.1016/0092-8674(84)90040-0. [DOI] [PubMed] [Google Scholar]
  2. Bentley D. R., Porter R. R. Isolation of cDNA clones for human complement component C2. Proc Natl Acad Sci U S A. 1984 Feb;81(4):1212–1215. doi: 10.1073/pnas.81.4.1212. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Campbell R. D., Bentley D. R., Morley B. J. The factor B and C2 genes. Philos Trans R Soc Lond B Biol Sci. 1984 Sep 6;306(1129):367–378. doi: 10.1098/rstb.1984.0097. [DOI] [PubMed] [Google Scholar]
  4. Campbell R. D., Porter R. R. Molecular cloning and characterization of the gene coding for human complement protein factor B. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4464–4468. doi: 10.1073/pnas.80.14.4464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Carroll M. C., Campbell R. D., Bentley D. R., Porter R. R. A molecular map of the human major histocompatibility complex class III region linking complement genes C4, C2 and factor B. Nature. 1984 Jan 19;307(5948):237–241. doi: 10.1038/307237a0. [DOI] [PubMed] [Google Scholar]
  6. Carroll M. C., Campbell R. D., Porter R. R. Mapping of steroid 21-hydroxylase genes adjacent to complement component C4 genes in HLA, the major histocompatibility complex in man. Proc Natl Acad Sci U S A. 1985 Jan;82(2):521–525. doi: 10.1073/pnas.82.2.521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Carroll M. C., Porter R. R. Cloning of a human complement component C4 gene. Proc Natl Acad Sci U S A. 1983 Jan;80(1):264–267. doi: 10.1073/pnas.80.1.264. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chaplin D. D., Sackstein R., Perlmutter D. H., Weis J. H., Kruse T. A., Coligan J., Colten H. R., Seidman J. G. Expression of hemolytically active murine fourth component of complement in transfected L cells. Cell. 1984 Jun;37(2):569–576. doi: 10.1016/0092-8674(84)90387-8. [DOI] [PubMed] [Google Scholar]
  9. Chaplin D. D., Woods D. E., Whitehead A. S., Goldberger G., Colten H. R., Seidman J. G. Molecular map of the murine S region. Proc Natl Acad Sci U S A. 1983 Nov;80(22):6947–6951. doi: 10.1073/pnas.80.22.6947. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Chu M. L., de Wet W., Bernard M., Ding J. F., Morabito M., Myers J., Williams C., Ramirez F. Human pro alpha 1(I) collagen gene structure reveals evolutionary conservation of a pattern of introns and exons. 1984 Jul 26-Aug 1Nature. 310(5975):337–340. doi: 10.1038/310337a0. [DOI] [PubMed] [Google Scholar]
  11. DiScipio R. G., Gehring M. R., Podack E. R., Kan C. C., Hugli T. E., Fey G. H. Nucleotide sequence of cDNA and derived amino acid sequence of human complement component C9. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7298–7302. doi: 10.1073/pnas.81.23.7298. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fey G. H., Lundwall A., Wetsel R. A., Tack B. F., de Bruijn M. H., Domdey H. Nucleotide sequence of complementary DNA and derived amino acid sequence of murine complement protein C3. Philos Trans R Soc Lond B Biol Sci. 1984 Sep 6;306(1129):333–344. doi: 10.1098/rstb.1984.0094. [DOI] [PubMed] [Google Scholar]
  13. Isenman D. E., Young J. R. The molecular basis for the difference in immune hemolysis activity of the Chido and Rodgers isotypes of human complement component C4. J Immunol. 1984 Jun;132(6):3019–3027. [PubMed] [Google Scholar]
  14. Lachmann P. J. Inherited complement deficiencies. Philos Trans R Soc Lond B Biol Sci. 1984 Sep 6;306(1129):419–430. doi: 10.1098/rstb.1984.0102. [DOI] [PubMed] [Google Scholar]
  15. Law S. K., Dodds A. W., Porter R. R. A comparison of the properties of two classes, C4A and C4B, of the human complement component C4. EMBO J. 1984 Aug;3(8):1819–1823. doi: 10.1002/j.1460-2075.1984.tb02052.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lundwall A., Wetsel R. A., Domdey H., Tack B. F., Fey G. H. Structure of murine complement component C3. I. Nucleotide sequence of cloned complementary and genomic DNA coding for the beta chain. J Biol Chem. 1984 Nov 25;259(22):13851–13856. [PubMed] [Google Scholar]
  17. Morley B. J., Campbell R. D. Internal homologies of the Ba fragment from human complement component Factor B, a class III MHC antigen. EMBO J. 1984 Jan;3(1):153–157. doi: 10.1002/j.1460-2075.1984.tb01776.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Nonaka M., Takahashi M., Natsuume-Sakai S., Nonaka M., Tanaka S., Shimizu A., Honjo T. Isolation of cDNA clones specifying the fourth component of mouse complement and its isotype, sex-limited protein. Proc Natl Acad Sci U S A. 1984 Nov;81(21):6822–6826. doi: 10.1073/pnas.81.21.6822. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ogata R. T., Sepich D. S. Genes for murine fourth complement component (C4) and sex-limited protein (Slp) identified by hybridization to C4- and Slp-specific cDNA. Proc Natl Acad Sci U S A. 1984 Aug;81(15):4908–4911. doi: 10.1073/pnas.81.15.4908. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ogata R. T., Shreffler D. C., Sepich D. S., Lilly S. P. cDNA clone spanning the alpha-gamma subunit junction in the precursor of the murine fourth complement component (C4). Proc Natl Acad Sci U S A. 1983 Aug;80(16):5061–5065. doi: 10.1073/pnas.80.16.5061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Palsdottir A., Cross S. J., Edwards J. H., Carroll M. C. Correlation between a DNA restriction fragment length polymorphism and C4A6 protein. Nature. 1983 Dec 8;306(5943):615–616. doi: 10.1038/306615a0. [DOI] [PubMed] [Google Scholar]
  22. Pangburn M. K., Müller-Eberhard H. J. The alternative pathway of complement. Springer Semin Immunopathol. 1984;7(2-3):163–192. doi: 10.1007/BF01893019. [DOI] [PubMed] [Google Scholar]
  23. Perlmutter D. H., Cole F. S., Goldberger G., Colten H. R. Distinct primary translation products from human liver mRNA give rise to secreted and cell-associated forms of complement protein C2. J Biol Chem. 1984 Aug 25;259(16):10380–10385. [PubMed] [Google Scholar]
  24. Podack E. R., Tschopp J. Membrane attack by complement. Mol Immunol. 1984 Jul;21(7):589–603. doi: 10.1016/0161-5890(84)90044-0. [DOI] [PubMed] [Google Scholar]
  25. Porter R. R. Complement polymorphism, the major histocompatibility complex and associated diseases: a speculation. Mol Biol Med. 1983 Jul;1(1):161–168. [PubMed] [Google Scholar]
  26. Porter R. R. The complement components of the major histocompatibility locus. CRC Crit Rev Biochem. 1984;16(1):1–19. doi: 10.3109/10409238409102804. [DOI] [PubMed] [Google Scholar]
  27. Reid K. B., Bentley D. R., Wood K. J. Cloning and characterization of the complementary DNA for the B chain of normal human serum C1q. Philos Trans R Soc Lond B Biol Sci. 1984 Sep 6;306(1129):345–354. doi: 10.1098/rstb.1984.0095. [DOI] [PubMed] [Google Scholar]
  28. Reid K. B., Porter R. R. The proteolytic activation systems of complement. Annu Rev Biochem. 1981;50:433–464. doi: 10.1146/annurev.bi.50.070181.002245. [DOI] [PubMed] [Google Scholar]
  29. Reid K. B. Proteins involved in the activation and control of the two pathways of human complement. Biochem Soc Trans. 1983 Jan;11(1):1–12. doi: 10.1042/bst0110001. [DOI] [PubMed] [Google Scholar]
  30. Rittner C., Bertrams J. On the significance of C2, C4, and factor B polymorphisms in disease. Hum Genet. 1981;56(3):235–247. doi: 10.1007/BF00274674. [DOI] [PubMed] [Google Scholar]
  31. Sackstein R., Colten H. R. Molecular regulation of MHC class III (C4 and factor B) gene expression in mouse peritoneal macrophages. J Immunol. 1984 Sep;133(3):1618–1626. [PubMed] [Google Scholar]
  32. Sackstein R., Colten H. R., Woods D. E. Phylogenetic conservation of a class III major histocompatibility complex antigen, factor B. Isolation and nucleotide sequencing of mouse factor B cDNA clones. J Biol Chem. 1983 Dec 10;258(23):14693–14697. [PubMed] [Google Scholar]
  33. Sackstein R., Roos M. H., Démant P., Colten H. R. Subdivision of the S region of the mouse major histocompatibility complex by identification of genomic polymorphisms of the class III genes. Immunogenetics. 1984;20(3):321–330. doi: 10.1007/BF00364213. [DOI] [PubMed] [Google Scholar]
  34. Stanley K. K., Kocher H. P., Luzio J. P., Jackson P., Tschopp J. The sequence and topology of human complement component C9. EMBO J. 1985 Feb;4(2):375–382. doi: 10.1002/j.1460-2075.1985.tb03639.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Stanley K. K., Luzio J. P. Construction of a new family of high efficiency bacterial expression vectors: identification of cDNA clones coding for human liver proteins. EMBO J. 1984 Jun;3(6):1429–1434. doi: 10.1002/j.1460-2075.1984.tb01988.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Steinmetz M., Hood L. Genes of the major histocompatibility complex in mouse and man. Science. 1983 Nov 18;222(4625):727–733. doi: 10.1126/science.6356354. [DOI] [PubMed] [Google Scholar]
  37. Takahashi S., Takahashi M., Kaidoh T., Natsuume-Sakai S., Takahashi T. Genetic mapping of mouse C4-bp locus to the H-2D-Qa interval. J Immunol. 1984 Jan;132(1):6–8. [PubMed] [Google Scholar]
  38. Wetsel R. A., Lundwall A., Davidson F., Gibson T., Tack B. F., Fey G. H. Structure of murine complement component C3. II. Nucleotide sequence of cloned complementary DNA coding for the alpha chain. J Biol Chem. 1984 Nov 25;259(22):13857–13862. [PubMed] [Google Scholar]
  39. Whitehead A. S., Colten H. R., Chang C. C., Demars R. Localization of the human MHC-linked complement genes between HLA-B and HLA-DR by using HLA mutant cell lines. J Immunol. 1985 Jan;134(1):641–643. [PubMed] [Google Scholar]
  40. Whitehead A. S., Goldberger G., Woods D. E., Markham A. F., Colten H. R. Use of a cDNA clone for the fourth component of human complement (C4) for analysis of a genetic deficiency of C4 in guinea pig. Proc Natl Acad Sci U S A. 1983 Sep;80(17):5387–5391. doi: 10.1073/pnas.80.17.5387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Whitehead A. S., Woods D. E., Fleischnick E., Chin J. E., Yunis E. J., Katz A. J., Gerald P. S., Alper C. A., Colten H. R. DNA polymorphism of the C4 genes. A new marker for analysis of the major histocompatibility complex. N Engl J Med. 1984 Jan 12;310(2):88–91. doi: 10.1056/NEJM198401123100204. [DOI] [PubMed] [Google Scholar]
  42. Wiebauer K., Domdey H., Diggelmann H., Fey G. Isolation and analysis of genomic DNA clones encoding the third component of mouse complement. Proc Natl Acad Sci U S A. 1982 Dec;79(23):7077–7081. doi: 10.1073/pnas.79.23.7077. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Woods D. E., Edge M. D., Colten H. R. Isolation of a complementary DNA clone for the human complement protein C2 and its use in the identification of a restriction fragment length polymorphism. J Clin Invest. 1984 Aug;74(2):634–638. doi: 10.1172/JCI111461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Woods D. E., Markham A. F., Ricker A. T., Goldberger G., Colten H. R. Isolation of cDNA clones for the human complement protein factor B, a class III major histocompatibility complex gene product. Proc Natl Acad Sci U S A. 1982 Sep;79(18):5661–5665. doi: 10.1073/pnas.79.18.5661. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. de Bruijn M. H., Fey G. H. Human complement component C3: cDNA coding sequence and derived primary structure. Proc Natl Acad Sci U S A. 1985 Feb;82(3):708–712. doi: 10.1073/pnas.82.3.708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. de Cordoba S. R., Ferreira A., Nussenzweig V., Rubinstein P. Genetic polymorphism of human C4-binding protein. J Immunol. 1983 Sep;131(3):1565–1569. [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES