Does the CDR3 of the heavy chain determine the specificity of autoantibodies in systemic lupus erythematosus?
Many factors are involved in the recognition of autoantigens by autoanti-bodies, including the use of specific germline genes, the sequence and structure of the CDR3 of the heavy chain, somatic mutation and selective heavy and light chain pairing. However, the relative importance of these factors remainsunclear. This study reports the results of sequence analysis of two anti-endothelial cell antibodies that recognise the same antigen. Sequence analysis of these antibodies shows that they use the same heavy chain germline genes as two anti-DNA antibodies but differ significantly in the sequence of the CDR3. Furthermore, one of the antibodies uses a light chain germline gene combination that has been reported for three anti-DNA antibodies. One of these antibodies shows significant mutation in the CDR2 of the heavy chain. Peptide analysis suggests that the differences between these anti-DNA and anti-endothelial cell antibodies result in consistent structural differences that may reflect the nature of the antigen recognised.
Yazici
Z A
ZA
Department of Biomedical Sciences, University of Bradford, Bradford, West Yorkshire, BD7 1DP, UK.
Behrendt
M
M
Goodfield
M
M
Partridge
L J
LJ
Lindsey
N J
NJ
D000595:Amino Acid Sequence; D000918:Antibody Specificity; D001323:Autoantibodies / Q000235:genetics / Q000276:immunology*; D001324:Autoantigens; D001483:Base Sequence; D022801:Complementarity Determining Regions; D017931:DNA Primers / Q000235:genetics; D005803:Genes, Immunoglobulin; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D007137:Immunoglobulin alpha-Chains / Q000235:genetics / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid
D001323:Autoantibodies; D001324:Autoantigens; D022801:Complementarity Determining Regions; D017931:DNA Primers; D007137:Immunoglobulin alpha-Chains