Selective cytotoxic T-lymphocyte targeting of tumor immune escape variants

Autor: Michael van der Veer, Per Grufman, Sandra A. Bres, Thorbald van Hall, Jan W. Drijfhout, Arnoud H. de Ru, Ferry Ossendorp, Sandra Laban, Rob Valentijn, Rienk Offringa, Kees L. M. C. Franken, Ad L. De Jong, Cornelis J. M. Melief, Frits Koning, Klas Kärre, Antoinette Teixeira, Elisabeth Z. Wolpert, Marjet Roseboom, Hans-Gustaf Ljunggren, Marcel Camps, Peter A. van Veelen, Hugo D. Meiring
Rok vydání: 2005
Předmět:
Antigen presentation
Molecular Sequence Data
Genes
MHC Class I
Immunoglobulins
chemical and pharmacologic phenomena
Mice
Inbred Strains
Biology
CD8-Positive T-Lymphocytes
Major histocompatibility complex
Immunotherapy
Adoptive
General Biochemistry
Genetics and Molecular Biology
Epitope
Antiporters
Epitopes
Mice
Antigen
Cell Line
Tumor
MHC class I
Cytotoxic T cell
Animals
Immunologic Surveillance
Cell Line
Transformed
Mice
Knockout
Antigen Presentation
Vaccines
Synthetic
Antigen processing
Histocompatibility Antigens Class I
Genetic Variation
Membrane Transport Proteins
General Medicine
Transporter associated with antigen processing
Cell Transformation
Viral
Cytotoxicity Tests
Immunologic
Clone Cells
Mice
Inbred C57BL
Cell Transformation
Neoplastic
Immunology
Gene Targeting
biology.protein
Tumor Escape
Immunotherapy
T-Lymphocytes
Cytotoxic
Zdroj: Nature medicine. 12(4)
ISSN: 1078-8956
Popis: Defects in major histocompatibility complex (MHC) class I-restricted antigen presentation are frequently observed in human cancers and result in escape of tumors from cytotoxic T lymphocyte (CTL) immune surveillance in mice. Here, we show the existence of a unique category of CTLs that can prevent this escape. The CTLs target an alternative repertoire of peptide epitopes that emerge in MHC class I at the surface of cells with impaired function of transporter associated with antigen processing (TAP), tapasin or the proteasome. These peptides, although derived from self antigens such as the commonly expressed Lass5 protein (also known as Trh4), are not presented by normal cells. This explains why they act as immunogenic neoantigens. The newly discovered epitopes can be exploited for immune intervention against processing-deficient tumors through adoptive T-cell transfer or peptide vaccination.
Databáze: OpenAIRE
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