Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1994 May;62(5):1776–1786. doi: 10.1128/iai.62.5.1776-1786.1994

Variable region sequences and idiotypic expression of a protective human immunoglobulin M antibody to capsular polysaccharides of Neisseria meningitidis group B and Escherichia coli K1.

F H Azmi 1, A H Lucas 1, H V Raff 1, D M Granoff 1
PMCID: PMC186406  PMID: 8168940

Abstract

We determined the heavy (H)- and light (L)-chain variable (V) region nucleotide and translated amino acid sequences of the human immunoglobulin M(kappa) monoclonal antibody (MAb) 5E1, which is specific for the polysaccharide capsule of Escherichia coli K1 and Neisseria meningitidis group B (poly[alpha(2-->8)-N-acetylneuraminic acid]) and which is protective in animal models of infection. The 5E1 VH gene is a member of the VHIIIb family and is 97% homologous to the 9.1 germ line gene. The 5E1 VL gene is a member of the kappa I subgroup and is 98% homologous to the germ line gene, 15A, also known as KLO12. The VL and/or VH genes used by 5E1 are highly homologous to the V genes encoding antibodies to the Haemophilus influenzae type b polysaccharide and to antibodies reactive with self-antigens such as erythrocyte "i," DNA, and thyroid peroxidase. We also produced three murine anti-idiotype (Id) MAbs against 5E1. All three anti-Ids recognize a minor subset of antimeningococcal B polysaccharide antibodies present in serum from normal adults. Two of the anti-Ids define distinct Ids associated with antibodies having kappa I-15A V regions. These 15A-associated Ids are expressed by some heterologous human antimeningococcal B polysaccharide MAbs, and they also are independently expressed by two human MAbs that are specific for either the H. influenzae b polysaccharide or the i erythrocyte antigen and that utilize the kappa I-15A V region. Taken together, these data indicate that the 5E1 antibody uses V regions that recur in the human antibody repertoires to this polysaccharide and to structurally dissimilar polysaccharides and autoantigens. Thus, the poor immunogenicity of poly[alpha(2-->8)-N-acetylneuraminic acid] cannot be explained by the unavailability of certain critical VH and VL genes required for generation of antibody response.

Full text

PDF
1776

Selected References

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

  1. Adderson E. E., Azmi F. H., Wilson P. M., Shackelford P. G., Carroll W. L. The human VH3b gene subfamily is highly polymorphic. J Immunol. 1993 Jul 15;151(2):800–809. [PubMed] [Google Scholar]
  2. Adderson E. E., Shackelford P. G., Insel R. A., Quinn A., Wilson P. M., Carroll W. L. Immunoglobulin light chain variable region gene sequences for human antibodies to Haemophilus influenzae type b capsular polysaccharide are dominated by a limited number of V kappa and V lambda segments and VJ combinations. J Clin Invest. 1992 Mar;89(3):729–738. doi: 10.1172/JCI115649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Adderson E. E., Shackelford P. G., Quinn A., Carroll W. L. Restricted Ig H chain V gene usage in the human antibody response to Haemophilus influenzae type b capsular polysaccharide. J Immunol. 1991 Sep 1;147(5):1667–1674. [PubMed] [Google Scholar]
  4. Adderson E. E., Shackelford P. G., Quinn A., Wilson P. M., Cunningham M. W., Insel R. A., Carroll W. L. Restricted immunoglobulin VH usage and VDJ combinations in the human response to Haemophilus influenzae type b capsular polysaccharide. Nucleotide sequences of monospecific anti-Haemophilus antibodies and polyspecific antibodies cross-reacting with self antigens. J Clin Invest. 1993 Jun;91(6):2734–2743. doi: 10.1172/JCI116514. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Artenstein M. S., Brandt B. L., Tramont E. C., Branche W. C., Jr, Fleet H. D., Cohen R. L. Serologic studies of meningococcal infection and polysaccharide vaccination. J Infect Dis. 1971 Sep;124(3):277–288. doi: 10.1093/infdis/124.3.277. [DOI] [PubMed] [Google Scholar]
  6. Aucouturier P., Bauwens M., Khamlichi A. A., Denoroy L., Spinelli S., Touchard G., Preud'homme J. L., Cogné M. Monoclonal Ig L chain and L chain V domain fragment crystallization in myeloma-associated Fanconi's syndrome. J Immunol. 1993 Apr 15;150(8 Pt 1):3561–3568. [PubMed] [Google Scholar]
  7. Berman J. E., Mellis S. J., Pollock R., Smith C. L., Suh H., Heinke B., Kowal C., Surti U., Chess L., Cantor C. R. Content and organization of the human Ig VH locus: definition of three new VH families and linkage to the Ig CH locus. EMBO J. 1988 Mar;7(3):727–738. doi: 10.1002/j.1460-2075.1988.tb02869.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chacko A., Granoff D. M. In vitro induction of IgG1 and IgG2 secretion by B cells of children who developed invasive haemophilus disease despite vaccination. Pediatr Res. 1991 Jul;30(1):124–129. doi: 10.1203/00006450-199107000-00024. [DOI] [PubMed] [Google Scholar]
  9. Chazenbalk G. D., Portolano S., Russo D., Hutchison J. S., Rapoport B., McLachlan S. Human organ-specific autoimmune disease. Molecular cloning and expression of an autoantibody gene repertoire for a major autoantigen reveals an antigenic immunodominant region and restricted immunoglobulin gene usage in the target organ. J Clin Invest. 1993 Jul;92(1):62–74. doi: 10.1172/JCI116600. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dersimonian H., Schwartz R. S., Barrett K. J., Stollar B. D. Relationship of human variable region heavy chain germ-line genes to genes encoding anti-DNA autoantibodies. J Immunol. 1987 Oct 1;139(7):2496–2501. [PubMed] [Google Scholar]
  11. Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Finne J., Leinonen M., Mäkelä P. H. Antigenic similarities between brain components and bacteria causing meningitis. Implications for vaccine development and pathogenesis. Lancet. 1983 Aug 13;2(8346):355–357. doi: 10.1016/s0140-6736(83)90340-9. [DOI] [PubMed] [Google Scholar]
  13. Frasch C. E. Vaccines for prevention of meningococcal disease. Clin Microbiol Rev. 1989 Apr;2 (Suppl):S134–S138. doi: 10.1128/cmr.2.suppl.s134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gawinowicz M. A., Merlini G., Birken S., Osserman E. F., Kabat E. A. Amino acid sequence of the FV region of a human monoclonal IgM (NOV) with specificity for the capsular polysaccharide of the group B meningococcus and of Escherichia coli K1, which cross-reacts with polynucleotides and with denatured DNA. J Immunol. 1991 Aug 1;147(3):915–920. [PubMed] [Google Scholar]
  15. Granoff D. M., Shackelford P. G., Holmes S. J., Lucas A. H. Variable region expression in the antibody responses of infants vaccinated with Haemophilus influenzae type b polysaccharide-protein conjugates. Description of a new lambda light chain-associated idiotype and the relation between idiotype expression, avidity, and vaccine formulation. The Collaborative Vaccine Study Group. J Clin Invest. 1993 Mar;91(3):788–796. doi: 10.1172/JCI116298. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Griffiss J. M., Brandt B. L., Broud D. D., Goroff D. K., Baker C. J. Immune response of infants and children to disseminated infections with Neisseria meningitidis. J Infect Dis. 1984 Jul;150(1):71–79. doi: 10.1093/infdis/150.1.71. [DOI] [PubMed] [Google Scholar]
  17. Hasemann C. A., Capra J. D. Mutational analysis of arsonate binding by a CRIA+ antibody. VH and VL junctional diversity are essential for binding activity. J Biol Chem. 1991 Apr 25;266(12):7626–7632. [PubMed] [Google Scholar]
  18. Hoare D. G., Koshland D. E., Jr A method for the quantitative modification and estimation of carboxylic acid groups in proteins. J Biol Chem. 1967 May 25;242(10):2447–2453. [PubMed] [Google Scholar]
  19. Huang D. F., Olee T., Masuho Y., Matsumoto Y., Carson D. A., Chen P. P. Sequence analyses of three immunoglobulin G anti-virus antibodies reveal their utilization of autoantibody-related immunoglobulin Vh genes, but not V lambda genes. J Clin Invest. 1992 Dec;90(6):2197–2208. doi: 10.1172/JCI116105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Jeske D. J., Jarvis J., Milstein C., Capra J. D. Junctional diversity is essential to antibody activity. J Immunol. 1984 Sep;133(3):1090–1092. [PubMed] [Google Scholar]
  21. Joshi A. K., Baichwal V., Ames G. F. Rapid polymerase chain reaction amplification using intact bacterial cells. Biotechniques. 1991 Jan;10(1):42, 44-5. [PubMed] [Google Scholar]
  22. Kasper D. L., Winkelhake J. L., Zollinger W. D., Brandt B. L., Artenstein M. S. Immunochemical similarity between polysaccharide antigens of Escherichia coli 07: K1(L):NM and group B Neisseria meningitidis. J Immunol. 1973 Jan;110(1):262–268. [PubMed] [Google Scholar]
  23. Kearney J. F., Radbruch A., Liesegang B., Rajewsky K. A new mouse myeloma cell line that has lost immunoglobulin expression but permits the construction of antibody-secreting hybrid cell lines. J Immunol. 1979 Oct;123(4):1548–1550. [PubMed] [Google Scholar]
  24. Kim K. S., Cross A. S., Zollinger W., Sadoff J. Prevention and therapy of experimental Escherichia coli infection with monoclonal antibody. Infect Immun. 1985 Dec;50(3):734–737. doi: 10.1128/iai.50.3.734-737.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kim K. S., Itabashi H., Gemski P., Sadoff J., Warren R. L., Cross A. S. The K1 capsule is the critical determinant in the development of Escherichia coli meningitis in the rat. J Clin Invest. 1992 Sep;90(3):897–905. doi: 10.1172/JCI115965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Lifely M. R., Roberts S. C., Shepherd W. M., Esdaile J., Wang Z., Cleverly A., Aulaqi A. A., Moreno C. Immunogenicity in adult males of a Neisseria meningitidis group B vaccine composed of polysaccharide complexed with outer membrane proteins. Vaccine. 1991 Jan;9(1):60–66. doi: 10.1016/0264-410x(91)90318-z. [DOI] [PubMed] [Google Scholar]
  27. Liu T. Y., Gotschlich E. C., Dunne F. T., Jonssen E. K. Studies on the meningococcal polysaccharides. II. Composition and chemical properties of the group B and group C polysaccharide. J Biol Chem. 1971 Aug 10;246(15):4703–4712. [PubMed] [Google Scholar]
  28. Lucas A. H., Granoff D. M. A major crossreactive idiotype associated with human antibodies to the Haemophilus influenzae b polysaccharide. Expression in relation to age and immunoglobulin G subclass. J Clin Invest. 1990 Apr;85(4):1158–1166. doi: 10.1172/JCI114548. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Lucas A. H., Langley R. J., Granoff D. M., Nahm M. H., Kitamura M. Y., Scott M. G. An idiotypic marker associated with a germ-line encoded kappa light chain variable region that predominates the vaccine-induced human antibody response to the Haemophilus influenzae b polysaccharide. J Clin Invest. 1991 Dec;88(6):1811–1818. doi: 10.1172/JCI115502. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Matthyssens G., Rabbitts T. H. Structure and multiplicity of genes for the human immunoglobulin heavy chain variable region. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6561–6565. doi: 10.1073/pnas.77.11.6561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Messing J. New M13 vectors for cloning. Methods Enzymol. 1983;101:20–78. doi: 10.1016/0076-6879(83)01005-8. [DOI] [PubMed] [Google Scholar]
  32. Moreno C., Lifely M. R., Esdaile J. Immunity and protection of mice against Neisseria meningitidis group B by vaccination, using polysaccharide complexed with outer membrane proteins: a comparison with purified B polysaccharide. Infect Immun. 1985 Feb;47(2):527–533. doi: 10.1128/iai.47.2.527-533.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Pargent W., Meindl A., Thiebe R., Mitzel S., Zachau H. G. The human immunoglobulin kappa locus. Characterization of the duplicated O regions. Eur J Immunol. 1991 Aug;21(8):1821–1827. doi: 10.1002/eji.1830210807. [DOI] [PubMed] [Google Scholar]
  34. Peltola H. Meningococcal disease: still with us. Rev Infect Dis. 1983 Jan-Feb;5(1):71–91. doi: 10.1093/clinids/5.1.71. [DOI] [PubMed] [Google Scholar]
  35. Pinner R. W., Gellin B. G., Bibb W. F., Baker C. N., Weaver R., Hunter S. B., Waterman S. H., Mocca L. F., Frasch C. E., Broome C. V. Meningococcal disease in the United States--1986. Meningococcal Disease Study Group. J Infect Dis. 1991 Aug;164(2):368–374. doi: 10.1093/infdis/164.2.368. [DOI] [PubMed] [Google Scholar]
  36. Potter H., Weir L., Leder P. Enhancer-dependent expression of human kappa immunoglobulin genes introduced into mouse pre-B lymphocytes by electroporation. Proc Natl Acad Sci U S A. 1984 Nov;81(22):7161–7165. doi: 10.1073/pnas.81.22.7161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Quagliarello V., Scheld W. M. Bacterial meningitis: pathogenesis, pathophysiology, and progress. N Engl J Med. 1992 Sep 17;327(12):864–872. doi: 10.1056/NEJM199209173271208. [DOI] [PubMed] [Google Scholar]
  38. Raff H. V., Bradley C., Brady W., Donaldson K., Lipsich L., Maloney G., Shuford W., Walls M., Ward P., Wolff E. Comparison of functional activities between IgG1 and IgM class-switched human monoclonal antibodies reactive with group B streptococci or Escherichia coli K1. J Infect Dis. 1991 Feb;163(2):346–354. doi: 10.1093/infdis/163.2.346. [DOI] [PubMed] [Google Scholar]
  39. Raff H. V., Devereux D., Shuford W., Abbott-Brown D., Maloney G. Human monoclonal antibody with protective activity for Escherichia coli K1 and Neisseria meningitidis group B infections. J Infect Dis. 1988 Jan;157(1):118–126. doi: 10.1093/infdis/157.1.118. [DOI] [PubMed] [Google Scholar]
  40. Rougon G., Dubois C., Buckley N., Magnani J. L., Zollinger W. A monoclonal antibody against meningococcus group B polysaccharides distinguishes embryonic from adult N-CAM. J Cell Biol. 1986 Dec;103(6 Pt 1):2429–2437. doi: 10.1083/jcb.103.6.2429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Sanz I., Dang H., Takei M., Talal N., Capra J. D. VH sequence of a human anti-Sm autoantibody. Evidence that autoantibodies can be unmutated copies of germline genes. J Immunol. 1989 Feb 1;142(3):883–887. [PubMed] [Google Scholar]
  43. Sarff L. D., McCracken G. H., Schiffer M. S., Glode M. P., Robbins J. B., Orskov I., Orskov F. Epidemiology of Escherichia coli K1 in healthy and diseased newborns. Lancet. 1975 May 17;1(7916):1099–1104. doi: 10.1016/s0140-6736(75)92496-4. [DOI] [PubMed] [Google Scholar]
  44. Schneerson R., Bradshaw M., Whisnant J. K., Myerowitz R. L., Parke J. C., Jr, Robbins J. B. An Escherichia coli antigen cross-reactive with the capsular polysaccharide of Haemophilus influenzae type b: occurrence among known serotypes, and immunochemical and biologic properties of E. coli antisera toward H. influenzae type b. J Immunol. 1972 Jun;108(6):1551–1562. [PubMed] [Google Scholar]
  45. Schroeder H. W., Jr, Wang J. Y. Preferential utilization of conserved immunoglobulin heavy chain variable gene segments during human fetal life. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6146–6150. doi: 10.1073/pnas.87.16.6146. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Schwartz B., Moore P. S., Broome C. V. Global epidemiology of meningococcal disease. Clin Microbiol Rev. 1989 Apr;2 (Suppl):S118–S124. doi: 10.1128/cmr.2.suppl.s118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Scott M. G., Crimmins D. L., McCourt D. W., Zocher I., Thiebe R., Zachau H. G., Nahm M. H. Clonal characterization of the human IgG antibody repertoire to Haemophilus influenzae type b polysaccharide. III. A single VKII gene and one of several JK genes are joined by an invariant arginine to form the most common L chain V region. J Immunol. 1989 Dec 15;143(12):4110–4116. [PubMed] [Google Scholar]
  48. Shlomchik M. J., Marshak-Rothstein A., Wolfowicz C. B., Rothstein T. L., Weigert M. G. The role of clonal selection and somatic mutation in autoimmunity. 1987 Aug 27-Sep 2Nature. 328(6133):805–811. doi: 10.1038/328805a0. [DOI] [PubMed] [Google Scholar]
  49. Sierra G. V., Campa H. C., Varcacel N. M., Garcia I. L., Izquierdo P. L., Sotolongo P. F., Casanueva G. V., Rico C. O., Rodriguez C. R., Terry M. H. Vaccine against group B Neisseria meningitidis: protection trial and mass vaccination results in Cuba. NIPH Ann. 1991 Dec;14(2):195–210. [PubMed] [Google Scholar]
  50. Silberstein L. E., Jefferies L. C., Goldman J., Friedman D., Moore J. S., Nowell P. C., Roelcke D., Pruzanski W., Roudier J., Silverman G. J. Variable region gene analysis of pathologic human autoantibodies to the related i and I red blood cell antigens. Blood. 1991 Nov 1;78(9):2372–2386. [PubMed] [Google Scholar]
  51. Skevakis L., Frasch C. E., Zahradnik J. M., Dolin R. Class-specific human bactericidal antibodies to capsular and noncapsular surface antigens of Neisseria meningitidis. J Infect Dis. 1984 Mar;149(3):387–396. doi: 10.1093/infdis/149.3.387. [DOI] [PubMed] [Google Scholar]
  52. Stephens D. S., Swartley J. S., Kathariou S., Morse S. A. Insertion of Tn916 in Neisseria meningitidis resulting in loss of group B capsular polysaccharide. Infect Immun. 1991 Nov;59(11):4097–4102. doi: 10.1128/iai.59.11.4097-4102.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Sutton A., Vann W. F., Karpas A. B., Stein K. E., Schneerson R. An avidin-biotin based ELISA for quantitation of antibody to bacterial polysaccharides. J Immunol Methods. 1985 Oct 10;82(2):215–224. doi: 10.1016/0022-1759(85)90353-9. [DOI] [PubMed] [Google Scholar]
  54. Wyle F. A., Artenstein M. S., Brandt B. L., Tramont E. C., Kasper D. L., Altieri P. L., Berman S. L., Lowenthal J. P. Immunologic response of man to group B meningococcal polysaccharide vaccines. J Infect Dis. 1972 Nov;126(5):514–521. doi: 10.1093/infdis/126.5.514. [DOI] [PubMed] [Google Scholar]
  55. Yanisch-Perron C., Vieira J., Messing J. Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors. Gene. 1985;33(1):103–119. doi: 10.1016/0378-1119(85)90120-9. [DOI] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES