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A spliced antigenic peptide comprising a single spliced amino acid is produced in the proteasome by reverse splicing of a longer peptide fragment followed by trimming.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2014 Feb 15; Vol. 192 (4), pp. 1962-71. Date of Electronic Publication: 2014 Jan 22. - Publication Year :
- 2014
-
Abstract
- Peptide splicing is a novel mechanism of production of peptides relying on the proteasome and involving the linkage of fragments originally distant in the parental protein. Peptides produced by splicing can be presented on class I molecules of the MHC and recognized by CTLs. In this study, we describe a new antigenic peptide, which is presented by HLA-A3 and comprises two noncontiguous fragments of the melanoma differentiation Ag gp100(PMEL17) spliced together in the reverse order to that in which they appear in the parental protein. Contrary to the previously described spliced peptides, which are produced by the association of fragments of 3-6 aa, the peptide described in this work results from the ultimate association of an 8-aa fragment with a single arginine residue. As described before, peptide splicing takes place in the proteasome by transpeptidation involving an acyl-enzyme intermediate linking one of the peptide fragment to a catalytic subunit of the proteasome. Interestingly, we observe that the peptide causing the nucleophilic attack on the acyl-enzyme intermediate must be at least 3 aa long to give rise to a spliced peptide. The spliced peptide produced from this reaction therefore bears an extended C terminus that needs to be further trimmed to produce the final antigenic peptide. We show that the proteasome is able to perform the final trimming step required to produce the antigenic peptide described in this work.
- Subjects :
- Animals
COS Cells
Cell Line, Tumor
Chlorocebus aethiops
HLA-A3 Antigen genetics
HLA-A3 Antigen immunology
HLA-A3 Antigen metabolism
Humans
Melanoma genetics
Melanoma immunology
Peptide Fragments genetics
T-Lymphocytes, Cytotoxic immunology
gp100 Melanoma Antigen immunology
gp100 Melanoma Antigen metabolism
Melanoma metabolism
Proteasome Endopeptidase Complex metabolism
Protein Splicing physiology
gp100 Melanoma Antigen genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 192
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 24453253
- Full Text :
- https://doi.org/10.4049/jimmunol.1302032