Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 41, Issue 11, Pages 3114-3124Publisher
WILEY
DOI: 10.1002/eji.201141836
Keywords
Antigen processing; Cytotoxic T lymphocytes; Transporter associated with peptide processing
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Funding
- Portuguese Foundation For Science and Technology (MCTES) Portugal [SFRH/BD/33539/2008]
- AICR [09-776]
- Dutch Cancer Society [UL 2007-3897]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/33539/2008] Funding Source: FCT
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We recently described a category of TAP-independent peptide-epitopes that are selectively presented by cells with processing defects in the classical MHC class I (MHC-I) pathway. Here, we studied the ER-resident ceramide synthase Trh4 as a prototypic example of these neo-antigens and found that moderate inhibition of TAP permits cell surface presentation of the Trh4 peptide. The absence of this peptide from WT cells was not related to the binding or stability of the Trh4/D-b complexes, or to the availability of MHC-I heavy chains, but rather to the limited expression of the antigen. Strongly elevated antigen levels were needed to reach comparable peptide display on WT as on TAP-deficient cells. Our data suggest that the normal influx of TAP-transported peptides in the ER during routine processing creates an efficient barrier for peptides from alternative processing routes. Impairment of TAP function, as commonly found in cancers and virus-infected cells, lowers this resistance allowing for MHC-I presentation of other peptide sources.
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