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, Sebastian & Radwan 2019), partially support the TCR depletion hypothesis, but also suggest additional, unexplored mechanisms that might be constraining expansion of the MHC gene family.