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 autoan tibodies, including the use of specific germline genes, the sequence a nd structure of the CDR3 of the heavy chain, somatic mutation and sele ctive heavy and light chain pairing. However, the relative importance of these factors remains unclear. This study reports the results of se quence analysis of two antiendothelial cell antibodies that recognise the same antigen. Sequence analysis of these antibodies shows that the y use the same heavy chain germline genes as two anti-DNA antibodies b ut differ significantly in the sequence of the CDR3. Furthermore, one of the antibodies uses a light chain germline gene combination that ha s been reported for three anti-DNA antibodies. One of these antibodies shows significant mutation in the CDR2 of the heavy chain. Peptide an alysis suggests that the differences between these anti-DNA and anti-e ndothelial cell antibodies result in consistent structural differences that may reflect the nature of the antigen recognised. (C) 1998 Acade mic Press