Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Proteins bearing an endoplasmic reticulum (ER) leader are inserted into the ER followed by cleavage of the signal peptide. Major histocompatibility complex class I-restricted T-cell epitopes can be generated from these proteins by the proteasome after retrotranslocation into the cytosol. Here, we show that an HLA-A(*)0201-restricted epitope from prostate stem cell antigen contains the cleavage site of the ER signal peptidase. The resulting cleavage products fail to bind to HLA-A(*)0201 and are not recognized by T lymphocytes. As processing of prostate stem cell antigen by signal peptidase occurs immediately after co-translational insertion, the epitope must be processed from polypeptides that have never reached the ER. The processing of this epitope depends on the proteasome and the transporter associated with antigen processing and shows a novel pathway of class I processing that relies on the failure of ER-targeted proteins to reach their target compartment.

Original publication

DOI

10.1038/sj.embor.7401065

Type

Journal article

Journal

EMBO Rep

Publication Date

10/2007

Volume

8

Pages

945 - 951

Keywords

Antigen Presentation, Antigens, Neoplasm, Cell Line, Endoplasmic Reticulum, GPI-Linked Proteins, Histocompatibility Antigens Class I, Humans, Major Histocompatibility Complex, Membrane Glycoproteins, Membrane Proteins, Neoplasm Proteins, Proteasome Endopeptidase Complex, Recombinant Fusion Proteins, Serine Endopeptidases, Signal Transduction, T-Lymphocytes, Cytotoxic, Transfection