About this Research Topic
CD8+ T cells recognize peptides presented by MHC class I molecules (MHC-I) while MHC class II molecules (MHC-II) present peptides to CD4+ T lymphocytes. The source of ligands, and the pathways involved in their generation, are different for these two MHC molecules.
The MHC-I peptide ligands are generated during the catabolism of nuclear and cytoplasmic proteins. The standard processing pathway involves protein degradation by the proteasome. The resulting peptides are transported to the lumen of the endoplasmic reticulum (ER) through the dedicated peptide transporter TAP, where they can be processed by aminopeptidase ERAP to generate the final MHC-I ligand. Antigen processing for MHC-II presentation takes place, however, in the vesicular compartment and mots MHC-II-associated peptides derive from proteins located in the cell vesicles, membrane proteins, or external proteins. The invariant chain (Ii) is important to avoid the loading of peptides in the ER and to direct the MHC-II molecules to a specialized endolysosomal compartment. Ii chain is enzymatically degraded except CLIP, which remains into the binding site. DM catalyzes the replacement of CLIP with high-affinity peptides. The resulting peptide–MHC class I and peptide–MHC class II complexes travel to the cell surface to be presented to T lymphocytes.
The components of class I and class II antigen processing pathways have been described and new components added along the time. In addition, some alternative processing events have been defined during the last decades, through the introduction of new components (TAPBPR, DO, etc.), proteasome-independent pathways (involving other proteases as TPPII, furin, etc.), TAP-independent pathways or new activities of the previously known proteins of the pathways (the putative generation of spliced peptides by the proteasome, etc.).
The topic of surface presentation of peptides by MHC molecules has become more complex than it was thought to be decades ago. MHC peptide repertoires are very complex, composed of thousands of peptides, and that diversity is substantially increased through the effects of post-translational modification, generating nonstandard residues (phosphorylated, citrullinated, carbonylated, etc.). Different MHC allotypes have distinct peptide-binding motifs, which can be more or less restricted and exhibit diverse preferences for standard and nonstandard amino acids.
Finally, the presentation of peptides in healthy or disease tissues can vary, depending on many aspects: intrinsic antigen processing of specific cells (as β cells in diabetes), inflammation (as citrullination in rheumatoid arthritis, etc.
The goal of this Research Topic is to shed new light into alternative antigen processing including new components of the routes. Additionally, new insights on motifs and binding preferences of specific MHC I and MHC II are of interest.
We welcome the submission of Original Research, Methods, Reviews, and Mini-Reviews that cover recent advances in the following topics:
- Alternative antigen processing produced by new functions of the components of the MHC-I or MHC-II pathways.
- Antigen processing role of new or recently discovered components of the antigen processing pathways.
- Alternative processing pathways involving other components than the standard ones.
- New insights on the MHC peptide motifs and repertoires.
- Alternative antigen processing or presentation in specific tissues.
- Alternative antigen processing or presentation in health and disease.
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