title: Susceptibility of amphibians to chytridiomycosis is associated with MHC class II conformation.
abstract: The pathogenic chytrid fungus Batrachochytrium dendrobatidis (Bd) can cause precipitous population declines in its amphibian hosts. Responses of individuals to infection vary greatly with the capacity of their immune system to respond to the pathogen. We used a combination of comparative and experimental approaches to identify major histocompatibility complex class II (MHC-II) alleles encoding molecules that foster the survival of Bd-infected amphibians. We found that Bd-resistant amphibians across four continents share common amino acids in three binding pockets of the MHC-II antigen-binding groove. Moreover, strong signals of selection acting on these specific sites were evident among all species co-existing with the pathogen. In the laboratory, we experimentally inoculated Australian tree frogs with Bd to test how each binding pocket conformation influences disease resistance. Only the conformation of MHC-II pocket 9 of surviving subjects matched those of Bd-resistant species. This MHC-II conformation thus may determine amphibian resistance to Bd, although other MHC-II binding pockets also may contribute to resistance. Rescuing amphibian biodiversity will depend on our understanding of amphibian immune defence mechanisms against Bd. The identification of adaptive genetic markers for Bd resistance represents an important step forward towards that goal.
authors: Laboratory of Behavioral and Population Ecology, School of Biological Sciences, Seoul National University, Seoul 151-747, South Korea.
authors: Arnaud
authors: A
authors: Bataille
authors: School of Public Health, Tropical Medicine and Rehabilitation Sciences, James Cook University, Townsville, Queensland 4811, Australia.
authors: Scott D
authors: SD
authors: Cashins
authors: School of Public Health, Tropical Medicine and Rehabilitation Sciences, James Cook University, Townsville, Queensland 4811, Australia.
authors: Laura
authors: http://orcid.org/0000-0002-2553-7598
authors: L
authors: Grogan
authors: School of Public Health, Tropical Medicine and Rehabilitation Sciences, James Cook University, Townsville, Queensland 4811, Australia.
authors: Lee F
authors: LF
authors: Skerratt
authors: New South Wales Office of Environment and Heritage, Biodiversity Conservation Section, Queanbeyan, New South Wales 2620, Australia.
authors: David
authors: D
authors: Hunter
authors: Taronga Conservation Society Australia, Herpetofauna Division, Mosman, New South Wales 2088, Australia.
authors: Michael
authors: M
authors: McFadden
authors: Fenner School of Environment and Society, Australian National University, Acton, Australian Capital Territory 2601, Australia.
authors: Benjamin
authors: B
authors: Scheele
authors: School of Public Health, Tropical Medicine and Rehabilitation Sciences, James Cook University, Townsville, Queensland 4811, Australia.
authors: Laura A
authors: LA
authors: Brannelly
authors: Fenner School of Environment and Society, Australian National University, Acton, Australian Capital Territory 2601, Australia.
authors: Amy
authors: A
authors: Macris
authors: Taronga Conservation Society Australia, Herpetofauna Division, Mosman, New South Wales 2088, Australia.
authors: Peter S
authors: PS
authors: Harlow
authors: School of Public Health, Tropical Medicine and Rehabilitation Sciences, James Cook University, Townsville, Queensland 4811, Australia.
authors: Sara
authors: S
authors: Bell
authors: School of Public Health, Tropical Medicine and Rehabilitation Sciences, James Cook University, Townsville, Queensland 4811, Australia.
authors: Lee
authors: L
authors: Berger
authors: Laboratory of Behavioral and Population Ecology, School of Biological Sciences, Seoul National University, Seoul 151-747, South Korea waldman@snu.ac.kr.
authors: Bruce
authors: http://orcid.org/0000-0003-0006-5333
authors: B
authors: Waldman
mesh_terms: D056704:Adaptive Immunity; D000595:Amino Acid Sequence; D029845:Amphibian Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001001:Anura / Q000235:genetics / Q000378:metabolism; D008411:Chytridiomycota / Q000502:physiology*; D060467:Disease Resistance; D004198:Disease Susceptibility; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009181:Mycoses / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000662:veterinary*; D016415:Sequence Alignment / Q000662:veterinary
chemical_list: D029845:Amphibian Proteins; D000949:Histocompatibility Antigens Class II
keywords: conservation; disease resistance; emerging infectious disease; major histocompatibility complex; peptide-binding domain; pocket residue