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A High Throughput MHC II Binding Assay for Quantitative Analysis of Peptide Epitopes
07:59

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Published on: March 25, 2014

Efficient MHC class I-independent amino-terminal trimming of epitope precursor peptides in the endoplasmic reticulum

D Fruci1, G Niedermann, R H Butler

  • 1Institut National de la Santé et de la Recherche Médicale, Unité 25, 75015 Paris, France.

Immunity
|September 25, 2001
PubMed

MHC class I ligands are produced mainly by proteasomal proteolysis, in conjunction with an unknown extent of trimming by peptidases. Trimming of precursor peptides in the endoplasmic reticulum, a process postulated to be class I dependent, may substantially enhance the efficiency of antigen presentation. However, monitoring of luminal peptide processing has not so far been possible. Here we show that several precursor peptides with amino-terminal extensions are rapidly converted to HLA-A2 ligands by one or several highly efficient metallo-peptidases found on the outer surface of, but also within, microsomes. Surprisingly, luminal trimming is fully active in HLA class I- or TAP-deficient microsomes and precedes peptide association with HLA class I molecules. Trimmed peptides are rapidly depleted from, and become undetectable in, microsomes lacking the restricting class I molecules.

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