A New Antigenic Epitope Localized Within Human κLight Chains Specific for Rheumatoid Arthritis and Systemic Lupus Erythematosus

Landenberg, Philipp von; Landenberg, C von; Gründl, Martin; Schmitz, Gerd; Schölmerich, Jürgen; Melchers, Inga

doi:10.1006/jaut.1999.0290

Cited by 4 publications

(2 citation statements)

References 14 publications

(19 reference statements)

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“…In the case of rheumatoid arthritis, a new peptide epitope RASFp1 has recently been identified from utilizing an IgG1 lambda monoclonal antibody to rheumatoid factor. In this case, it was concluded that the RASFp1‐binding antibody's subtle conformational changes may very well convert a normal IgG molecule to recognize autoantigen that it normally would ignore 33,34. Also noted was the possibility for differing specificities of antibodies in recognizing the identical epitope.…”

Section: Discussionmentioning

confidence: 98%

Peptide Mimics of a Major Lupus Epitope of SmB/B′

Kaufman

Kirby

Harley

et al. 2003

Annals of the New York Academy of Sciences

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One of the most distinguishing features of systemic lupus erythematosus is the presence of high concentrations of autoantibodies that recognize a limited number of self-antigens. Even though many lupus autoantigens have been identified, the inciting triggers of these abnormal immune responses are not fully understood. One mechanism that could generate these autoantibodies is a normal immune response toward a foreign epitope that mimics a common antigenic target of an autoantigen. Antibody generated toward the foreign epitope could also bind the autoantigen. This "cross-reactivity" would result in the presentation of the autoantigen to the immune system. Under autoimmune-prone conditions, tolerance toward the native protein is broken and an autoimmune response is initiated. Previously, it was suggested that Epstein-Barr virus might use such a mechanism to initiate an autoimmune response. Cross-reactive epitopes may have a similar amino acid sequence or a similar tertiary structure that is independent of amino acid sequence. A major, and likely initial, target of the lupus anti-SmB' response is a repeated, proline-rich sequence, PPPGMRPP. To identify potential cross-reactive targets, we used affinity-purified autoantibodies specific for PPPGMRPP to screen a random heptapeptide phage display library. Eighty-five clones were isolated and sequenced with eleven distinct sequence motifs being identified. Two of these motifs were homologous to the SmB' epitope, while the other nine were not. Interestingly, one of the peptide motifs that mimicked the SmB' epitope is identical to a peptide sequence found in the Epstein-Barr virus major DNA binding protein.

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