Home LiteratureArticle Details
PMID: 2452836 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Complete protein sequences of the variable regions of the cloned heavy and light chains of a human anti-cytomegalovirus antibody reveal a striking similarity to human monoclonal rheumatoid factors of the Wa idiotypic family.

The Journal of clinical investigation ·Vol. 81 ·No. 5 ·1988-05-00 ·Pages 1511-8

Newkirk MM, Gram H, Heinrich GF, Ostberg L, Capra JD, Wasserman RL

Abstract

The complete amino acid and nucleotide sequences of the variable regions of the heavy and light polypeptide chains of a human neutralizing IgGl anti-cytomegalovirus (CMV) antibody reveal a striking homology to IgM rheumatoid factors (RFs) of the Wa idiotypic family. The anti-CMV antibody and Wa RFs have in common VKIIIb, JKl, and VHIa gene segments but use different DH and JH gene segments. The anti-CMV antibody does not have RF activity and does not express the Wa idiotype. The Wa RFs do not have anti-CMV activity. A subset of Wa RFs, however, and the anti-CMV antibody do share several idiotypes on the VHIa and VKIIIb polypeptides. Since there are major differences in the antigen binding characteristics and some of the other expressed idiotypes, these data suggest that the D and J region amino acids are crucial to such specificities. Although the use of such highly homologous gene segments in different immune responses is well-documented in murine systems, these data represent the first such example in the human.

MeSH Terms
Amino Acid Sequence Antibodies, Viral/genetics Antibody Specificity Base Sequence Cytomegalovirus/genetics,immunology DNA/genetics Epitopes Humans Immunoglobulin G/genetics Immunoglobulin Heavy Chains/genetics Immunoglobulin Idiotypes/genetics Immunoglobulin Light Chains/genetics Immunoglobulin Variable Region/genetics Molecular Sequence Data Nucleic Acid Hybridization Rheumatoid Factor/genetics Sequence Homology, Nucleic Acid
Chemicals
Antibodies, Viral Epitopes Immunoglobulin G Immunoglobulin Heavy Chains Immunoglobulin Idiotypes Immunoglobulin Light Chains Immunoglobulin Variable Region DNA Rheumatoid Factor
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Newkirk M M
Department of Microbiology, University of Texas Health Sciences Center, Dallas 75235.
Gram H
Heinrich G F
Ostberg L
Capra J D
Wasserman R L
References (62)
62 references, click to expand
  1. Prospective study of early rheumatoid arthritis. II. Association of rheumatoid factor isotypes with fluctuations in disease activity.
    Ann Rheum Dis. 1984 Oct;43(5):679-85 PMID: 6497460
  2. Cross-idiotypic specificity among monoclonal IgM proteins with anti- -globulin activity.
    J Exp Med. 1973 Feb 1;137(2):331-42 PMID: 4119588
  3. Complete amino acid sequences of variable regions of two human IgM rheumatoid factors, BOR and KAS of the Wa idiotypic family, reveal restricted use of heavy and light chain variable and joining region gene segments.
    J Exp Med. 1987 Aug 1;166(2):550-64 PMID: 2439644
  4. Bence Jones proteins and light chains of immunoglobulins. II. Immunochemical differentiation and classification of kappa-chains.
    J Exp Med. 1969 Dec 1;130(6):1295-311 PMID: 4187526
  5. Immunochemical similarities between monoclonal antibacterial Waldenstrom's macroglobulins and monoclonal anti-DNA lupus autoantibodies.
    J Exp Med. 1985 Jun 1;161(6):1525-38 PMID: 3925065
  6. Synthetic peptides corresponding to third hypervariable region of human monoclonal IgM rheumatoid factor heavy chains define an immunodominant idiotype.
    J Exp Med. 1985 Aug 1;162(2):756-61 PMID: 3926939
  7. Amino acid sequence of a light chain variable region of a human rheumatoid factor of the Wa idiotypic group, in part predicted by its reactivity with antipeptide antibodies.
    Mol Immunol. 1986 Mar;23(3):239-44 PMID: 3086710
  8. Sequence similarities and cross-idiotypic specificity of L chains among human monoclonal IgM kappa with anti-gamma-globulin activity.
    J Immunol. 1985 Dec;135(6):4073-9 PMID: 2415598
  9. A new protocol to digest human IgM with papain that results in homogeneous Fab preparations that can be routinely crystallized.
    Hybridoma. 1987 Oct;6(5):453-60 PMID: 3679258
  10. The VKIIIb light chain sub-subgroup: restricted association with mu heavy chain in normal human serum.
    Immunology. 1985 Feb;54(2):207-13 PMID: 3917972
  11. Correlation of antibody to rheumatoid arthritis associated nuclear antigen and immune complexes to disease activity in patients with rheumatoid arthritis.
    Clin Exp Immunol. 1983 Feb;51(2):278-84 PMID: 6601550
  12. Isolation of cytomegalovirus from synovial cells of a patient with rheumatoid arthritis.
    J Rheumatol. 1982 Sep-Oct;9(5):658-64 PMID: 6294295
  13. Similarities in the light chains of anti-gamma-globulins showing cross-idiotypic specificities.
    J Exp Med. 1974 Jan 1;139(1):128-36 PMID: 4543460
  14. Antiidiotypic activity in the IgM fractions of mixed cryoglobulins.
    J Immunol. 1980 Oct;125(4):1530-5 PMID: 6774023
  15. Cloned human and mouse kappa immunoglobulin constant and J region genes conserve homology in functional segments.
    Cell. 1980 Nov;22(1 Pt 1):197-207 PMID: 6775818
  16. Association of the B-cell alloantigen DRw4 with rheumatoid arthritis.
    N Engl J Med. 1978 Apr 20;298(16):869-71 PMID: 147420
  17. Amino acid sequence of the variable regions of heavy chains from two idiotypically cross-reactive human IgM anti-gamma-globulins of the Wa group.
    Biochemistry. 1981 Sep 29;20(20):5822-30 PMID: 7028111
  18. Antibodies to the Epstein-Barr virus nuclear antigen and to rheumatoid arthritis nuclear antigen identify the same polypeptide.
    Proc Natl Acad Sci U S A. 1983 Dec;80(23):7104-8 PMID: 6316343
  19. A highly conserved determinant on human rheumatoid factor idiotypes defined by a mouse monoclonal antibody.
    Eur J Immunol. 1983 Mar;13(3):197-201 PMID: 6187582
  20. IgM, IgG and IgA rheumatoid factors and circulating immune complexes in patients with AIDS and AIDS-related complex with serological abnormalities.
    Clin Exp Immunol. 1987 Feb;67(2):236-44 PMID: 3608224
  21. Genetic basis for the cross-reactive idiotypes on the light chains of human IgM anti-IgG autoantibodies.
    Proc Natl Acad Sci U S A. 1986 Nov;83(21):8318-22 PMID: 3095834
  22. Human rheumatoid factor crossidiotypes. I. WA and BLA are heat-labile conformational antigens requiring both heavy and light chains.
    J Exp Med. 1986 Nov 1;164(5):1809-14 PMID: 3095482
  23. Rubella-virus infection in juvenile rheumatoid arthritis.
    Lancet. 1975 May 24;1(7917):1157-61 PMID: 48775
  24. Human rheumatoid factor crossidiotypes. II. Primary structure-dependent crossreactive idiotype, PSL2-CRI, present on Wa monoclonal rheumatoid factors is present on Bla and other IgM kappa monoclonal autoantibodies.
    J Exp Med. 1987 Jan 1;165(1):263-7 PMID: 3098895
  25. Rheumatoid arthritis and generalized vaccinia.
    JAMA. 1978 Feb 20;239(8):747-8 PMID: 621896
  26. Individual Antigenic Specificity of Isolated Antibodies.
    Science. 1963 Jun 14;140(3572):1218-9 PMID: 17837506
  27. Anti-hypervariable region antibody induced by a defined peptide: an approach for studying the structural correlates of idiotypes.
    Proc Natl Acad Sci U S A. 1984 Mar;81(6):1784-8 PMID: 6200884
  28. Human immunoglobulin D segments encoded in tandem multigenic families.
    Nature. 1981 Dec 17;294(5842):631-5 PMID: 7312051
  29. Virus antibody levels and delayed hypersensitivity in rheumatoid arthritis.
    Ann Rheum Dis. 1976 Apr;35(2):152-4 PMID: 182092
  30. A common idiotope on human rheumatoid factors identified by a hybridoma antibody.
    Mol Immunol. 1983 Oct;20(10):1081-7 PMID: 6201726
  31. Evolutionary aspects of immunoglobulin heavy chain variable region (VH) gene subgroups.
    Proc Natl Acad Sci U S A. 1983 Feb;80(3):855-9 PMID: 6298778
  32. Evidence of similar idiotypic determinants on different rheumatoid factor populations.
    Scand J Immunol. 1979 Mar;9(3):281-9 PMID: 86204
  33. Rhesus monkey responses to multiple injections of human monoclonal antibodies.
    Hybridoma. 1987 Apr;6(2):151-60 PMID: 3494660
  34. Preferential secretion of a common anti-DNA idiotype (16/6 Id) and anti-polynucleotide antibodies by normal mononuclear cells following stimulation with Klebsiella pneumoniae.
    Immunol Lett. 1986 Jun;12(5-6):313-9 PMID: 3525398
  35. A technique for the removal of pyroglutamic acid from the amino terminus of proteins using calf liver pyroglutamate amino peptidase.
    Biochem Biophys Res Commun. 1978 Mar 15;81(1):176-85 PMID: 26343
  36. Somatic mutation creates diversity in the major group of mouse immunoglobulin kappa light chains.
    J Exp Med. 1984 Feb 1;159(2):417-35 PMID: 6420501
  37. A study of rubella haemagglutination inhibition antibodies in rheumatoid arthritis.
    Clin Exp Immunol. 1970 Jun;6(6):885-9 PMID: 5477727
  38. Structure of human immunoglobulin gamma genes: implications for evolution of a gene family.
    Cell. 1982 Jun;29(2):671-9 PMID: 6811139
  39. Preferential association of kappa IIIb light chains with monoclonal human IgM kappa autoantibodies.
    J Immunol. 1983 Sep;131(3):1322-5 PMID: 6193185
  40. Evidence for a subset of rheumatoid factors that cross-react with DNA-histone and have a distinct cross-idiotype.
    J Exp Med. 1980 Jun 1;151(6):1514-27 PMID: 6155424
  41. A seroepidemiological study of cytomegalovirus and Epstein-Barr virus in rheumatoid arthritis and sicca syndrome.
    Ann Rheum Dis. 1985 Nov;44(11):742-6 PMID: 2998290
  42. Clonally restricted anti-IgG antibodies in rheumatoid arthritis.
    Arthritis Rheum. 1984 Dec;27(12):1378-86 PMID: 6334525
  43. The molecular basis for HLA class II associations with rheumatoid arthritis.
    J Clin Immunol. 1987 Jan;7(1):1-7 PMID: 3558732
  44. Dissection of the human antigammaglobulin idiotype system with monoclonal antibodies.
    Scand J Immunol. 1986 Feb;23(2):169-81 PMID: 2419964
  45. A cloned human immunoglobulin heavy chain gene with a novel direct-repeat sequence in 5' flanking region.
    Gene. 1985;33(2):181-9 PMID: 3922855
  46. Inheritance of immunoglobulin M rheumatoid-factor idiotypes.
    J Clin Invest. 1980 Oct;66(4):863-6 PMID: 7419724
  47. A common anti-DNA idiotype in sera of patients with active pulmonary tuberculosis.
    Arthritis Rheum. 1987 Jan;30(1):50-6 PMID: 3814197
  48. Immunogenic and antigenic epitopes of immunoglobulins. XVII--Monoclonal antibodies reactive with common and restricted idiotopes to the heavy chain of human rheumatoid factors.
    Rheumatol Int. 1986;6(4):179-83 PMID: 2431452
  49. Virologic studies on rheumatoid arthritis.
    Arthritis Rheum. 1973 Jul-Aug;16(4):446-54 PMID: 4722429
  50. Crystallization of immunoglobulins and their fragments for X-ray diffraction studies.
    Methods Enzymol. 1985;116:190-200 PMID: 4088083
  51. Somatic mutation of the T15 heavy chain gives rise to an antibody with autoantibody specificity.
    Proc Natl Acad Sci U S A. 1984 Sep;81(18):5841-4 PMID: 6435121
  52. Structure of the human immunoglobulin mu locus: characterization of embryonic and rearranged J and D genes.
    Cell. 1981 Dec;27(3 Pt 2):583-91 PMID: 6101209
  53. Restricted light chain subgroup expression on human rheumatoid factor paraproteins determined by monoclonal antibodies.
    Immunology. 1986 Nov;59(3):473-8 PMID: 2432001
  54. Identifying infectious etiologies of chronic disease.
    Rev Infect Dis. 1984 Mar-Apr;6(2):200-13 PMID: 6374835
  55. IgM rheumatoid factor elaboration by blood, bone marrow, and synovial mononuclear cells in patients with rheumatoid arthritis.
    Clin Immunol Immunopathol. 1985 Mar;34(3):387-91 PMID: 3871679
  56. Delineation of a cross-reactive idiotype on human autoantibodies with antibody against a synthetic peptide.
    J Exp Med. 1984 May 1;159(5):1502-11 PMID: 6201589
  57. Evolution of human immunoglobulin kappa J region genes.
    J Biol Chem. 1982 Feb 10;257(3):1516-22 PMID: 6276389
  58. Lymphocytes transformed by Epstein-Barr virus. Induction of nuclear antigen reactive with antibody in rheumatoid arthritis.
    J Exp Med. 1978 Apr 1;147(4):1018-27 PMID: 206643
  59. Complete amino acid sequence of variable domains from two monoclonal human anti-gamma globulins of the Wa cross-idiotypic group: suggestion that the J segments are involved in the structural correlate of the idiotype.
    Proc Natl Acad Sci U S A. 1981 Jun;78(6):3799-803 PMID: 6167990
  60. Cold-reactive rheumatoid factors in infectious mononucleosis and other diseases.
    Arthritis Rheum. 1969 Apr;12(2):67-73 PMID: 4888035
  61. Junctional diversity is essential to antibody activity.
    J Immunol. 1984 Sep;133(3):1090-2 PMID: 6747289
  62. Cellular localization of rheumatoid factor idiotypes.
    J Clin Invest. 1982 Jun;69(6):1356-65 PMID: 6979553
Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
Published
1988-05-00
Pages
1511-8
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC442584
Subset
IM
Grants
NIAID NIH HHS · AI-12127 · United States
NIGMS NIH HHS · GM-31689 · United States
Databases
GENBANK
M20003, M20031
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]