Unconventional antigen presentation: atypical cells and unusual pathways

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Background

The presentation of antigens to T cells involves different cell types and different cellular pathways. In the classical view of antigen presentation, professional antigen presenting cells (APC), mainly dendritic cells (DC) present endogenous antigens to CD8 T cells and exogenous antigens to CD4 T cells. Classically epitopes loaded at the cell surface by MHC class II molecules (MHCII) are derived from internalized exogenous antigens that are processed in the endocytic compartment. In parallel epitopes that are loaded at the cell surface by MHC class I (MHCI) involve the proteasome and TAP peptide transporter.
However in addition to this classical view of antigen presentation, many studies have now described other routes and distinct cell types in antigen processing and presentation, supporting the fact that non-canonical antigen presentation plays a crucial role during the immune response, not only during the priming phase in secondary lymphoid organs but also during the effector phase in targets organs. These alternatives pathways can be particularly essential in the context of the anti-infectious or anti-tumoral T cell response but also in shaping the diversity of the T cell repertoire.
Recent evidence in the contribution of many other non-professional APC types, from both hematopoietic and non-hematopoietic origins, challenges the exclusive contribution of dendritic cells in priming a T cell response. In particular plasmacytoid DCs, granulocytes, stromal cells, epithelial cells and endothelial cells have all been described to be involved in antigen presentation to T cells.
In addition the description of atypical intracellular and intercellular pathways for antigenic peptide presentation, has dramatically changed and complexified our understanding of antigen recognition by T cells. In particular by using cross-presentation and autophagy routes APCs are able to load epitopes from both endogenous and exogenous source on MHCI and MHCII molecules, broadening the diversity and origin of their peptide sources.
These different strategies, combined to the classical ones, contribute to the generation of a functional and self-tolerant T cell repertoire in the thymus, and importantly to the development of immune responses in secondary lymphoid organs, in different settings such as pathogen infections and autoimmunity.
Therefore atypical peptide-MHC complexes, unconventional APC types and novel cellular pathways have completely changed our classical view of antigen presentation and T cell priming.
This Research Topic will cover all aspects of non–conventional antigen presentation and highlight their major contribution to the immune response.

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