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  • Review Article
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A guide to antigen processing and presentation

Abstract

Antigen processing and presentation are the cornerstones of adaptive immunity. B cells cannot generate high-affinity antibodies without T cell help. CD4+ T cells, which provide such help, use antigen-specific receptors that recognize major histocompatibility complex (MHC) molecules in complex with peptide cargo. Similarly, eradication of virus-infected cells often depends on cytotoxic CD8+ T cells, which rely on the recognition of peptide–MHC complexes for their action. The two major classes of glycoproteins entrusted with antigen presentation are the MHC class I and class II molecules, which present antigenic peptides to CD8+ T cells and CD4+ T cells, respectively. This Review describes the essentials of antigen processing and presentation. These pathways are divided into six discrete steps that allow a comparison of the various means by which antigens destined for presentation are acquired and how the source proteins for these antigens are tagged for degradation, destroyed and ultimately displayed as peptides in complex with MHC molecules for T cell recognition.

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Fig. 1: Simplified schematic maps of the MHC complex in humans, mice and chickens.
Fig. 2: Molecular models of classical MHC molecules and MHC-like molecules.
Fig. 3: Peptide splicing chemical reactions and anatomy of the proteasome.
Fig. 4: Trafficking pathways for MHC class I molecules.
Fig. 5: Trafficking pathways for MHC class II molecules.
Fig. 6: Organization and structure of the MHC peptide-loading complexes.

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Acknowledgements

The authors thank P. Cresswell and J. Strominger for reading an earlier version of the manuscript. They also thank members of the Ploegh laboratory for their input.

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Pishesha, N., Harmand, T.J. & Ploegh, H.L. A guide to antigen processing and presentation. Nat Rev Immunol 22, 751–764 (2022). https://doi.org/10.1038/s41577-022-00707-2

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