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The yin/yang balance of the MHC-self-immunopeptidome

Journal

FRONTIERS IN IMMUNOLOGY
Volume 13, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2022.1035363

Keywords

MHC class I; MHC class II; immune tolerance; regulatory T cells; antigen processing; antigen presentation; peptides

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This article summarizes the recognition of the MHC-self immunopeptidome by regulatory and conventional T cells under steady state and inflammatory conditions. It discusses how changes in the MHC-ligandome can affect the balance between pro-inflammatory and regulatory T cell expansion.
The MHC-self immunopeptidome of professional antigen presenting cells is a cognate ligand for the TCRs expressed on both conventional and thymic-derived natural regulatory T cells. In regulatory T cells, the TCR signaling associated with MHC-peptide recognition induces antigen specific as well as bystander immunosuppression. On the other hand, TCR activation of conventional T cells is associated with protective immunity. As such the peripheral T cell repertoire is populated by a number of T cells with different phenotypes and different TCRs, which can recognize the same MHC-self-peptide complex, resulting in opposite immunological outcomes. This article summarizes what is known about regulatory and conventional T cell recognition of the MHC-self-immunopeptidome at steady state and in inflammatory conditions associated with increased T and B cell self-reactivity, discussing how changes in the MHC-ligandome including epitope copy number and post-translational modifications can tilt the balance toward the expansion of pro-inflammatory or regulatory T cells.

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