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

Newkirk, Marianna M.; Chen, PP; Carson, Dennis A.; Posnett, David N.; Jd, Capra

doi:10.1016/0161-5890(86)90049-0

Cited by 20 publications

(7 citation statements)

References 23 publications

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“…The Humkv328 sequence is drawn from Chen et al [12] and the sequence for Vg and Vh are taken from Zachau et al [43]. The sequence for Gol was taken from Newkirk et al [36] and sequences for Bor and Kas were taken from Newkirk et al [37]. The notations (-) indicate positions of homology with Glo and (.)…”

Section: Genetic Basis For Cri Expressionmentioning

confidence: 99%

Idiotypes and the structural diversity of human rheumatoid factors

Fong

Chen

Crowley

et al. 1988

Springer Semin Immunopathol

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Section: Genetic Basis For Cri Expressionmentioning

confidence: 99%

Idiotypes and the structural diversity of human rheumatoid factors

Fong

Chen

Crowley

et al. 1988

Springer Semin Immunopathol

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“…The same idiotypic determinants are infrequently found (11,13,28,29). The proposed VK(RF) sequence (15) In summary, these experiments show that the crossreactive idiotypes on human RFs are phenotypic markers of a germ-line gene that is widespread in the normal human population.…”

Section: Resultsmentioning

confidence: 89%

Genetic basis for the cross-reactive idiotypes on the light chains of human IgM anti-IgG autoantibodies.

Chen¹,

Albrandt²,

Orida³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

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The role of immunoglobulin structural genes in the generation of autoantibodies in humans has not been elucidated. Human monoclonal IgM anti-IgG autoantibodies (rheumatoid factors, RFs) from unrelated people often share idiotypic antigens. Antibodies against synthetic peptides have localized two of the shared idiotypic determinants to the second and third complementarity-determining regions of the K light chain. The reported sequences of several human RF light chains are remarkably homologous in these regions. Animal studies have shown that some shared idiotypic antigens represent serological markers for immunoglobulin variable (V)-region genes. Therefore, we hypothesized that human RF light chains derived from a single germ-line gene, designated V -(RF), or from a small family of very closely related genes. In the present experiments, we have isolated and sequenced two human VK germ-line genes that encode K light chains, which are identical or closely related to the light chains of human RF. The data indicate that the shared idiotypic antigens on RF are phenotypic markers for a K V-region gene that is highly conserved in the human population. The results also imply that the light chains of IgM anti-IgG autoantibodies can be encoded by germ-line genes without any somatic mutation.Immune responses are controlled by genes that encode histocompatibility antigens, T-cell receptors for antigens, and immunoglobulins. The inherited structural genes for immunoglobulin light and heavy chains dictate the potential antibody repertoire of any individual. However, immunoglobulin genes also undergo extensive rearrangements and somatic mutations during life (1, 2). Both polymorphisms in inherited immunoglobulin genes as well as somatic changes may therefore influence the ability to form autoantibodies. To dissect the importance of the two factors, one must first isolate potential autoantibody structural genes in their germline configuration. This goal has proved difficult to accomplish in outbred human populations.Idiotypes are antigens in the variable (V) portion of immunoglobulins (3,4). In many instances, idiotypic antigens have been localized at or near the antigen binding site. Immunoglobulins that share idiotypic determinants often are related structurally and may represent the protein products of identical or similar antibody V-region genes (5-8).Kunkel and co-workers first demonstrated that several human monoclonal IgM anti-IgG autoantibodies (rheumatoid factors, RFs) from unrelated subjects shared idiotypic antigens (9). A majority of these monoclonal RFs also had homologous sequences in the K light-chain V regions (10-13). Subsequent experiments with anti-peptide antibodies localized two of the shared idiotypic determinants, also termed cross-reactive idiotypes, to the second and third complementarity-determining regions of the K light chain. After an analysis of multiple RF light chains with a diverse series of anti-idiotypic reagents, we postulated that the cross-reactive idiotypes were markers for a single...

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“…The heavy chain is of the VH-III subgroup and the kappa light chain is of the V-III subgroup. The kappa light chain of the V-III subgroup is found in a high percentage of monoclonal rheumatoid factors (Kunkel et al, 1974;Newkirk et al, 1986). The presence of a light chain of the V-III subgroup in hDP200 therefore indicates that it is a monoclonal rheumatoid factor.…”

Section: Discussionmentioning

confidence: 97%

Human decidua-associated protein hDP200 appears to be a rheumatoid factor

Halperin

Kraicer²,

Hadas³

1994

Reproduction

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The amino acid sequences of the amino-terminal of the two different polypeptide chains of the human decidua-associated protein hDP200, with apparent molecular masses of 55 and 25 kDa, were determined. The amino-terminal sequence of the 55 kDa chain revealed that it is an immunoglobulin heavy chain, of the VH-III subgroup and the amino-terminal sequence of the 25 kDa chain showed that it is a human kappa V-III light chain. The sequence data indicate that hDP200 is an immunoglobulin. The ability of the hDP200 molecules to form high molecular weight complexes with immunoglobulins of other classes suggest that hDP200 is a rheumatoid factor.

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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

Cited by 20 publications

References 23 publications

Idiotypes and the structural diversity of human rheumatoid factors

Idiotypes and the structural diversity of human rheumatoid factors

Genetic basis for the cross-reactive idiotypes on the light chains of human IgM anti-IgG autoantibodies.

Human decidua-associated protein hDP200 appears to be a rheumatoid factor

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