ISSN:
1573-4943
Keywords:
Autoantibodies
;
rheumatoid arthritis
;
T-cell receptor
;
IgM
;
CDR3 region
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract Natural autoantibodies to the T-cell receptor (Tcr) have been identified in all human sera. However, titer, epitope specificity, and isotype vary with physiological conditions, autoimmune diseases, and retroviral infections. The levels of anti-Tcr autoantibodies in rheumatoid arthritis (RA) patients are significantly higher than in normal individuals, and the autoantibodies are typically IgM. To obtain detailed information on these autoantibodies, we generated B-cell heterohybridomas secreting monoclonal IgM autoantibodies (mAAbs) from the synovial tissue and peripheral blood of RA patients. We selected clones secreting mAAbs that bound a major Vβ epitope defined by a synthetic peptide that contains the CDR1 region of the Vβ 8.1 gene product. From these we isolated a subset of seven mAAbs that bound a recombinant single-chain Vα/Vβ construct containing the peptide epitope and, also to JURKAT cells which express Vβ 8.1. The mAAbs produced by these clones were distinct from each other in their V-region sequences. However, all the V regions were essentially identical to germline sequences in both the heavy and light chains. Heavy-chain CDR3 segments ranged in length from 17 to 26 residues, did not correspond to any known autoantibodies, and showed extensive N-region diversity in the V(D)J junctions. Five monoclonal autoantibodies use VH 3 genes, while the remaining two utilized VH 4 sequences. Light-chain variable regions used were Vκ 3 (two), Vλ 3 (four), and one Vλ 2. These autoantibodies derived their unique features from their CDR3 segments that could not be aligned with any known sequences.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1007086608036
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