Monday, November 6, 2006

Splice and die!

drj writes "Cytotoxic T lymphocytes (CTL) are triggered by short peptides (8-10 amino acids) held by MHC class I molecules on the target cell. Peptides often derive from cleaved and trimmed full-length proteins but an
earlier report described a spliced peptide that flanks a 40 amino acid deletion within the protein fibroblast growth factor-5 (FGF-5). Vigneron et al. now report the second example of a spliced peptide, a 4 amino acid deletion within a melanocyte glycoprotein 100 (gp100) peptide. They also found that “highly purified” proteasomes are capable of peptide splicing and suggested that closely spaced threonines within the proteasome catalyze protein cleavage and peptide ligation. They estimate that only 1 spliced peptide is produced from 10,000 gp100 molecules but even this low efficiency is good enough to trigger CTL. This phenomenon expands enormously the universe of potential peptides (and will greatly complicate the prediction of MHC binding peptides).
PubMed An Antigenic Peptide Produced by Peptide Splicing in the Proteasome Vigneron N, Stroobant V, Chapiro J, Ooms A, Degiovanni G, Morel S, van der Bruggen P, Boon T, Van den Eynde BJ.
Science 304:587-23 APRIL 2004"

1 comment:

Anonymous said...

Inefficient but Sufficient --
The CTL specific for a spliced FGF-5 peptide in the earlier report were derived from a tumor that was shrinking (the tumor was removed at the same time as surgery to remove many other, growing tumors)(review []). This suggesting that the spliced peptide was an extraordinarily good tumor-specific antigen. Maybe it's worth looking harder for these rare but apparently effective peptides.