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

posted Feb 26, 2019, 6:17 AM by Jacek Radwan
The major histocompatibility complex (MHC) is central for self-/non–self-recognition and acquired immunity. The extreme polymorphism of MHC genes, promoted by parasite-mediated selection, contrasts with limited within-individual diversity. The prevailing explanation is a trade-off between increased pathogen recognition and the anti-autoimmune T cell receptor (TCR) depletion mechanism. However, the predicted inverse relationship between individual MHC diversity and TCR repertoire size has not yet been shown. Using a rodent species with a variable number of MHC genes, we detected such an effect for MHC class I, but not class II. Our results, reported in PNAS (Migalska et al. 2019), partially support the TCR depletion hypothesis, but also suggest additional, unexplored mechanisms that might be constraining expansion of the MHC gene family.