The major histocompatibility complex: a double-edged sword in fungal disease susceptibility

Chytridiomycosis, caused by Batrachochytrium dendrobatidis (Bd), threatens amphibian populations worldwide. MHC II has been implicated in Bd susceptibility, but the role of MHC in Bd susceptibility remains poorly understood. In this study, we clustered MHC II {beta}1 alleles into functional supertypes and investigated their diversity in amphibian species with differential susceptibility. Despite sharing similar alpha diversity in MHC II supertypes, the hosts exhibited distinct beta diversity. We demonstrated MHC supertypes can predict Bd susceptibility better than individual MHC alleles, with some supertypes conferring protection and others increasing risk. This suggests that MHC alleles function more as part of a complex network than as independent entities. We also quantified MHC allelic-specific expression and observed individual-level variability in expression across both species. Notably, positive and negative associations among MHC alleles were observed. The similarity of these patterns between the two species suggests the presence of conserved regulatory mechanisms across amphibians. Our results provide valuable resources and insights to advance the understanding of adaptive immunological systems and to develop targeted conservation strategies to preserve biodiversity.