Back to Search
Start Over
Processing of two latent membrane protein 1 MHC class I epitopes requires tripeptidyl peptidase II involvement
- Source :
- Journal of immunology (Baltimore, Md. : 1950). 183(3)
- Publication Year :
- 2009
-
Abstract
- The EBV Ag latent membrane protein 1 (LMP1) has been described as a potential target for T cell immunotherapy in EBV-related malignancies. However, only a few CD8+ T cell epitopes are known, and the benefit of LMP1-specific T cell immunotherapy has not yet been proven. In this work, we studied the processing of the two LMP1 HLA-A02-restricted epitopes, YLLEMLRWL and YLQQNWWTL. We found that target cells endogenously expressing the native LMP1 are not recognized by CTLs specific for these epitopes because the N-terminal part of LMP1 limits the efficiency of epitope generation. We further observed that the proteasome is not required for the generation of both epitopes and that the YLLEMLRWL epitope seems to be destroyed by the proteasome, because blocking of proteasomal activities enhanced specific CTL activation. Activation of LMP1-specific CTLs could be significantly reduced after inhibition of the tripeptidyl peptidase II, suggesting a role for this peptidase in the processing of both epitopes. Taken together, our results demonstrate that the MHC class I-restricted LMP1 epitopes studied in this work are two of very few epitopes known to date to be processed proteasome independently by tripeptidyl peptidase II.
- Subjects :
- Epstein-Barr Virus Infections
Proteasome Endopeptidase Complex
Lymphoma, B-Cell
Immunology
T-Cell Antigen Receptor Specificity
Aminopeptidases
Epitope
Latent Membrane Protein-1
Viral Matrix Proteins
T-Cell Epitopes
Epitopes
Cell Line, Tumor
MHC class I
HLA-A2 Antigen
otorhinolaryngologic diseases
Immunology and Allergy
Humans
Amino Acid Sequence
Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
Cell Line, Transformed
Antigen Presentation
biology
HLA-A Antigens
Chemistry
Histocompatibility Antigens Class I
Serine Endopeptidases
Tripeptidyl peptidase II
Molecular biology
Cell biology
stomatognathic diseases
CTL
Proteasome
biology.protein
CD8
T-Lymphocytes, Cytotoxic
Subjects
Details
- ISSN :
- 15506606
- Volume :
- 183
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Accession number :
- edsair.doi.dedup.....06f90628665999fe69f0467a22a2e619