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Publication Detail
Dual recognition of lipid A and DNA by human antibodies encoded by the VH4-21 gene: A possible link between infection and lupus
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    Spellerberg MB, Chapman CJ, Mockridge CI, Isenberg DA, Stevenson FK
  • Publication date:
    01/01/1995
  • Pagination:
    52, 56
  • Journal:
    Human Antibodies
  • Volume:
    6
  • Issue:
    2
  • Status:
    Published
  • Print ISSN:
    1093-2607
Abstract
The VH4-21 (V4-34) gene segment, a member of the VH4 family, is expressed early in B-cell maturation and is utilized by approximately 6% of normal adult B lymphocytes. This prevalence indicates an importance of VH4-21 in the B-cell repertoire. The gene also encodes certain autoantibodies being mandatory for pathological IgM anti-red cell antibodies directed against the Iii antigen, and also capable of encoding anti-DNA antibodies. Recognition of I/i antigen or DNA appears to be via two distinct sites on VHwith I/i binding mediated by sequences in the framework region, and DNA binding correlating with the presence of positively charged amino acids in complementarity-determining region 3. However, these positively charged residues appear to suppress the ability of the framework region to interact with Iii, rendering a single sequence monospecific for I/i or DNA. The IgM anti-DNA antibodies also recognize bacterial lipid A, whereas the anti-I/i antibodies do not, indicating that CDR3 may be involved in binding the negatively charged lipid A. Structural similarities between the DNA backbone and lipid A provide a possible explanation for this cross-reactivity. This dual recognition of bacterial antigen and autoantigen provides a potential link between infection and autoimmunity. © 1995 Forefront Publishing (USA).
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