A subset of HLA-I peptides are not genomically templated: Evidence for cis- and trans-spliced peptide ligands

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Science Immunology  12 Oct 2018:
Vol. 3, Issue 28, eaar3947
DOI: 10.1126/sciimmunol.aar3947

Stitching peptides for presentation

Intracellular protein–derived peptides generated by proteasomal degradation are loaded on to class I MHC molecules in the endoplasmic reticulum and presented to CD8+ T cells. Although it has been assumed that these peptides are contiguous segments derived from intracellular proteins, recent studies have shown that noncontiguous peptides generated by cis-splicing of two distinct regions of an antigen can be presented by class I MHC molecules. Here, Faridi et al. demonstrate that class I MHC molecules can present peptides that are generated by splicing together of segments from two distinct proteins and term them to be “trans-spliced” peptides. Precisely how cis- and trans-spliced peptides are generated and how they contribute to T cell selection and expansion remain to be explored.

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