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A peptide's perspective on antigen presentation to the immune system

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Abstract

Specific immune responses are critically dependent on protein degradation products in the form of peptides. These peptides are presented by major histocompatibility complexes (MHCs), and recognition of MHC–peptide complexes by the immune system determines successful pathogen elimination, transplant rejection, autoimmunity or death. Here we review the immune response from the peptide's perspective and discuss the fate of peptides in cells before presentation by MHC complexes. We then discuss how peptides are altered post-translationally to yield immune responses and how peptides can be engineered to achieve strong immune responses following vaccination. Although peptides are simple from a chemical perspective, they are complex in their immunological consequences.

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Figure 1: The basics of peptide presentation by MHC molecules.
Figure 2: Peptides binding to MHC class I and II molecules.
Figure 3: Chemical alterations to alter MHC-peptide affinity and proteolytic stability.

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Acknowledgements

This work was supported by a Horizon grant from the Netherlands Genomics Initiative to H.O., a European Research Council advanced grant to J.N. and a Netherlands Organisation for Scientific Research–Chemische Wetenschappen (NWO-CW) TOP grant jointly to H.O. and J.N. We thank P. Celie and M. Garstka for help with figures.

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Correspondence to Jacques Neefjes or Huib Ovaa.

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Neefjes, J., Ovaa, H. A peptide's perspective on antigen presentation to the immune system. Nat Chem Biol 9, 769–775 (2013). https://doi.org/10.1038/nchembio.1391

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