Major histocompatibility complex class I diversity limits the repertoire of T cell receptors

Proceedings of the National Academy of Sciences of the United States of America
Magdalena MigalskaJacek Radwan

Abstract

Major histocompatibility complex (MHC) genes encode proteins that initiate adaptive immune responses through the presentation of foreign antigens to T cells. The high polymorphism found at these genes, thought to be promoted and maintained by pathogen-mediated selection, contrasts with the limited number of MHC loci found in most vertebrates. Although expressing many diverse MHC genes should broaden the range of detectable pathogens, it has been hypothesized to also cause deletion of larger fractions of self-reactive T cells, leading to a detrimental reduction of the T cell receptor (TCR) repertoire. However, a key prediction of this TCR depletion hypothesis, that the TCR repertoire should be inversely related to the individual MHC diversity, has never been tested. Here, using high-throughput sequencing and advanced sequencing error correction, we provide evidence of such an association in a rodent species with high interindividual variation in the number of expressed MHC molecules, the bank vole (Myodes glareolus). Higher individual diversity of MHC class I, but not class II, was associated with smaller TCR repertoires. Our results thus provide partial support for the TCR depletion model, while also highlighting the complex, p...Continue Reading

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Citations

May 17, 2019·PLoS Computational Biology·Piotr Bentkowski, Jacek Radwan
Feb 26, 2020·Proceedings. Biological Sciences·Piotr Bentkowski, Jacek Radwan
Apr 10, 2020·Frontiers in Immunology·Jing Wang, Bo Han
Sep 19, 2020·Immunity & Ageing : I & a·Chirag KrishnaTimothy A Chan
Feb 12, 2020·Trends in Genetics : TIG·Jacek RadwanJamie Winternitz
Mar 6, 2021·Evolution; International Journal of Organic Evolution·Emily A O'Connor, Helena Westerdahl
May 8, 2021·Molecular Ecology·Wei HuangJosephine M Pemberton
May 25, 2021·The Journal of Animal Ecology·Joanna Drzewińska-ChańkoPiotr Minias
Aug 17, 2021·Frontiers in Immunology·Daniil ShevyrevVladimir Kozlov
Aug 11, 2021·Molecular Biology and Evolution·Gemma PalomarWiesław Babik

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