Dual recognition of lipid A and DNA by human antibodies encoded by the VH4-21 gene: A possible link between infection and lupus
| Autor: | M B Spellerberg, Freda K. Stevenson, C I Mockridge, Caroline J. Chapman, D.A. Isenberg |
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| Rok vydání: | 1995 |
| Předmět: | |
| Zdroj: | Human Antibodies. 6:52-56 |
| ISSN: | 1875-869X 1093-2607 |
| DOI: | 10.3233/hab-1995-6203 |
| Popis: | 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 I/i antigen, and also capable of encoding anti-DNA antibodies. Recognition of I/i antigen or DNA appears to be via two distinct sites on VH, with 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 I/i, 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. |
| Databáze: | OpenAIRE |
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