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Publication : Selective cytotoxic T-lymphocyte targeting of tumor immune escape variants.

First Author  van Hall T Year  2006
Journal  Nat Med Volume  12
Issue  4 Pages  417-24
PubMed ID  16550190 Mgi Jnum  J:129530
Mgi Id  MGI:3769621 Doi  10.1038/nm1381
Citation  van Hall T, et al. (2006) Selective cytotoxic T-lymphocyte targeting of tumor immune escape variants. Nat Med 12(4):417-24
abstractText  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.
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