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From: "Making sense of mass destruction: quantitating MHC class I antigen presentation", Jonathan W. Yewdell, Eric Reits & Jacques Neefjes,
Nature Reviews Immunology 3, 952-961 (December 2003) doi:10.1038/nri1250
Courtesy Eric Reits
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HLA ligandome, antigen processing
The proteasome and several other proteases (some probably as yet unknown) play an important role in a continuous protein turn-over in the cell. As a result of this protein break down peptides may arise which might be translocated by the transporter associated with antigen presentation (TAP) into the endoplasmic reticulum (ER). In the ER peptides may be further trimmed and be loaded into HLA class I molecules. From there the peptide-loaded HLA-molecules are transported to the surface where they are on display to CD8+ T-lymphocytes. For further information see: references.
HLA-peptidome/ligandome & variation
HLA-presented peptides are generated from the proteome, derived from the consensus coding sequences and all possible variations.
Variation in the presented peptide repertoire may arise from translation in alternative reading frames, the occurence of non-synonymous SNPs, frameshifts, deletions and alternative splicing.
T cell epitopes
Altered presented peptides may elicit an immune response. Tumor antigens from ARFs and mHags are examples.
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