Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

A variety of unconventional translational and posttranslational mechanisms contribute to the production of antigenic peptides, thereby increasing the diversity of the peptide repertoire presented by MHC class I molecules. Here, we describe a class I-restricted peptide that combines several posttranslational modifications. It is derived from tyrosinase and recognized by tumor-infiltrating lymphocytes isolated from a melanoma patient. This unusual antigenic peptide is made of two noncontiguous tyrosinase fragments that are spliced together in the reverse order. In addition, it contains two aspartate residues that replace the asparagines encoded in the tyrosinase sequence. We confirmed that this peptide is naturally presented at the surface of melanoma cells, and we showed that its processing sequentially requires translation of tyrosinase into the endoplasmic reticulum and its retrotranslocation into the cytosol, where deglycosylation of the two asparagines by peptide-N-glycanase turns them into aspartates by deamidation. This process is followed by cleavage and splicing of the appropriate fragments by the standard proteasome and additional transport of the resulting peptide into the endoplasmic reticulum through the transporter associated with antigen processing (TAP).

Original publication

DOI

10.1073/pnas.1101892108

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

19/07/2011

Volume

108

Pages

E323 - E331

Keywords

Antibodies, Monoclonal, Antigen Presentation, Chemical Fractionation, Chromatography, High Pressure Liquid, Endoplasmic Reticulum, Histocompatibility Antigens Class I, Humans, Lymphocytes, Tumor-Infiltrating, Melanoma, Monophenol Monooxygenase, Peptides, Protein Processing, Post-Translational, Protein Transport