科研之友
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摘要
Anti-Sm antibodies, a specific marker for SLE, are directed against the B'/B and Dp polypeptides of Sm small nuclear ribonucleoproteins. The Y12 monoclonal anti-Sm antibody (Y12 mAb), as well as many anti-Sm patient sera, recognize cross-reactive epitopes on the B'/B and D polypeptides. This immunoreactive site is of special interest since polypeptides B and D share little amino acid sequence homology. In the present study, we have sought to establish the autoantigenic domain of polypeptides B and D that accounts for this epitope. We tested the ability of the Y12 mAb and anti-Sm sera to immunoprecipitate truncated forms of polypeptides B and D translated in vitro from mRNA bearing 5' and 3' end deletions. Most anti-Sm sera bound epitopes at the carboxyl-terminus of polypeptide B, however, autoantigenic epitopes were also found at the amino-terminus (amino acids 1 to 83 and 104 to 115). Surprisingly, the Y12 mAb recognized nonoverlapping amino-terminal and carboxyl-terminal halves of polypeptide B. One putative Y12 mAb binding site (amino acids 104 to 11 5) indicated by carboxyl-terminal deletion studies was confirmed through recognition of a corresponding synthetic peptide. Deletion studies with polypeptide D demonstrated a major autoantigenic domain on the carboxyl-terminus (amino acids 85 to 119) that was necessary for recognition by the Y12 mAb and by 7/14 patient sera. These results indicate that a cross-reactive epitope on B'/B and D, as defined by the Y12 mAb, resides on at least two different domains of polypeptide B and localizes to the carboxyl-terminus of polypeptide D. From the shared homology of truncated forms of B and D polypeptides recognizable with the Yl 2 mAb, we suspect that some form of GRG motif is involved in developing the Y12 mAb epitope that may involve other residues and be largely conformational in nature.
- 出版日期1993-4-15
