High affinity cross-reacting mAb generated by minimal mimicry: Implications for the pathogenesis of anti-nuclear autoantibodies and immunosuppression
AUTOR(ES)
Rothermel, Annette L.
FONTE
The National Academy of Sciences
RESUMO
The antigen recognition of a profoundly immunosuppressive mAb, mAb 2E1, in vivo was investigated. In addition to the 62-kDa effector cell protease receptor 1, mAb 2E1 bound the 32-kDa T cell adhesion receptor E2 (CD99) and the 86-kDa p80 subunit of the nuclear antigen complex Ku. These molecules share no overall sequence similarity. Peptide mapping experiments identified the mAb 2E1 cross-reacting epitopes as the sequences 66GSFSDADLAD75 in E2 and 571GGAHFSVSSLAEG583 in p80 of Ku, sharing a minimal homology motif FSXXXLA, in which X is a nonconserved amino acid. Each of these peptides separately inhibited the binding of mAb 2E1 to E2, effector cell protease receptor 1, and p80 of Ku in a dose-dependent manner. Scatchard plot analysis of 125I-labeled mAb 2E1 binding to peripheral blood mononuclear cells revealed a high-affinity interaction with a dissociation constant of 7 × 10−10 M. An anti-E2 mAb bound the same epitope 66GSFSDADLAD75 recognized by mAb 2E1 but failed to react with p80 of Ku and was not immunosuppressive. These findings demonstrate that high-affinity cross-reacting mAbs can be generated by mimicry of a minimal surface on unrelated molecules. This model of minimal mimicry may determine the nuclear reactivity of certain autoantibodies to Ku and contribute to aberrant immunosuppression in vivo.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=19920Documentos Relacionados
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