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Susceptibility of amphibians to chytridiomycosis is associated with MHC class II conformation.

Bataille A, Cashins SD, Grogan L, Skerratt LF, Hunter D, McFadden M, Scheele B, Brannelly LA, Macris A, Harlow PS, Bell S, Berger L, Waldman B - Proc. Biol. Sci. (2015)

Bottom Line: We found that Bd-resistant amphibians across four continents share common amino acids in three binding pockets of the MHC-II antigen-binding groove.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Behavioral and Population Ecology, School of Biological Sciences, Seoul National University, Seoul 151-747, South Korea.

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.

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Alignment of the β1 domain of the MHC class II in amphibiansillustrating peptide-binding residues. Each sequence in thealignment represents a consensus sequence grouping alleles isolatedin a species, or in a subgroup within species. Susceptibility ofeach was determined by experimental infections or field observationof Bd-associated population declines. Positions encoding amino acidssimilar to Bd-resistant Bufo gargarizans arerepresented by a dot. Variable positions in consensus sequences arerepresented by the most frequent amino acid in the group (lower caseletters). Dashes indicate missing data. Peptide-binding residues arehighlighted in colours, as denoted, to indicate their associationwith pockets of the MHC peptide-binding groove. Bd-resistantLitoria verreauxii alpina(Livea-R), Bd-susceptible L. v.alpina (Livea-S), Bufogargarizans (Buga), Bombinaorientalis (Boor), Bombinabombina (Bobo), Bombinavariegata (Bova), Bombinapachypus (Bopa), Bufobufo (Bubu), Bufo[Epidalea] calamita(Buca), Rana [Lithobates]yavapaiensis (Raya),Rana [Lithobates]catesbeiana (Raca),susceptible Rana spp. (sRana)including Rana [Lithobates]clamitans, R. pipiens,R. [Lithobates]sylvatica, R.[Lithobates] warszewitschiiand Rana temporaria, Alytesobstetricans (Alob), Xenopuslaevis (Xela), Andriasdavidianus (Anda), Ambystomamexicanum and A. tigrinum(Anme/Amti). Raya-Q, allelefrom Rana [Lithobates]yavapaiensis associated withBd resistance. The complete alignment with allMHC-II β1 included in the study is available in theelectronic supplementary material.
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RSPB20143127F1: Alignment of the β1 domain of the MHC class II in amphibiansillustrating peptide-binding residues. Each sequence in thealignment represents a consensus sequence grouping alleles isolatedin a species, or in a subgroup within species. Susceptibility ofeach was determined by experimental infections or field observationof Bd-associated population declines. Positions encoding amino acidssimilar to Bd-resistant Bufo gargarizans arerepresented by a dot. Variable positions in consensus sequences arerepresented by the most frequent amino acid in the group (lower caseletters). Dashes indicate missing data. Peptide-binding residues arehighlighted in colours, as denoted, to indicate their associationwith pockets of the MHC peptide-binding groove. Bd-resistantLitoria verreauxii alpina(Livea-R), Bd-susceptible L. v.alpina (Livea-S), Bufogargarizans (Buga), Bombinaorientalis (Boor), Bombinabombina (Bobo), Bombinavariegata (Bova), Bombinapachypus (Bopa), Bufobufo (Bubu), Bufo[Epidalea] calamita(Buca), Rana [Lithobates]yavapaiensis (Raya),Rana [Lithobates]catesbeiana (Raca),susceptible Rana spp. (sRana)including Rana [Lithobates]clamitans, R. pipiens,R. [Lithobates]sylvatica, R.[Lithobates] warszewitschiiand Rana temporaria, Alytesobstetricans (Alob), Xenopuslaevis (Xela), Andriasdavidianus (Anda), Ambystomamexicanum and A. tigrinum(Anme/Amti). Raya-Q, allelefrom Rana [Lithobates]yavapaiensis associated withBd resistance. The complete alignment with allMHC-II β1 included in the study is available in theelectronic supplementary material.

Mentions: The MHC-II β1 alleles of amphibian species least affected by Bd infection[21–25] consistently presented thesame amino acids, or amino acids with similar chemical properties, at all 15pocket residues (figure 1 andtable 1; electronicsupplementary material, figure S1). By contrast, these pocket-specific aminoacid compositions were less frequent in species susceptible to Bd [19,20] (P4: , p = 0.009; P6:, p < 0.001; P9:, p = 0.04; table 1). Figure 1.


Susceptibility of amphibians to chytridiomycosis is associated with MHC class II conformation.

Bataille A, Cashins SD, Grogan L, Skerratt LF, Hunter D, McFadden M, Scheele B, Brannelly LA, Macris A, Harlow PS, Bell S, Berger L, Waldman B - Proc. Biol. Sci. (2015)

Alignment of the β1 domain of the MHC class II in amphibiansillustrating peptide-binding residues. Each sequence in thealignment represents a consensus sequence grouping alleles isolatedin a species, or in a subgroup within species. Susceptibility ofeach was determined by experimental infections or field observationof Bd-associated population declines. Positions encoding amino acidssimilar to Bd-resistant Bufo gargarizans arerepresented by a dot. Variable positions in consensus sequences arerepresented by the most frequent amino acid in the group (lower caseletters). Dashes indicate missing data. Peptide-binding residues arehighlighted in colours, as denoted, to indicate their associationwith pockets of the MHC peptide-binding groove. Bd-resistantLitoria verreauxii alpina(Livea-R), Bd-susceptible L. v.alpina (Livea-S), Bufogargarizans (Buga), Bombinaorientalis (Boor), Bombinabombina (Bobo), Bombinavariegata (Bova), Bombinapachypus (Bopa), Bufobufo (Bubu), Bufo[Epidalea] calamita(Buca), Rana [Lithobates]yavapaiensis (Raya),Rana [Lithobates]catesbeiana (Raca),susceptible Rana spp. (sRana)including Rana [Lithobates]clamitans, R. pipiens,R. [Lithobates]sylvatica, R.[Lithobates] warszewitschiiand Rana temporaria, Alytesobstetricans (Alob), Xenopuslaevis (Xela), Andriasdavidianus (Anda), Ambystomamexicanum and A. tigrinum(Anme/Amti). Raya-Q, allelefrom Rana [Lithobates]yavapaiensis associated withBd resistance. The complete alignment with allMHC-II β1 included in the study is available in theelectronic supplementary material.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4389617&req=5

RSPB20143127F1: Alignment of the β1 domain of the MHC class II in amphibiansillustrating peptide-binding residues. Each sequence in thealignment represents a consensus sequence grouping alleles isolatedin a species, or in a subgroup within species. Susceptibility ofeach was determined by experimental infections or field observationof Bd-associated population declines. Positions encoding amino acidssimilar to Bd-resistant Bufo gargarizans arerepresented by a dot. Variable positions in consensus sequences arerepresented by the most frequent amino acid in the group (lower caseletters). Dashes indicate missing data. Peptide-binding residues arehighlighted in colours, as denoted, to indicate their associationwith pockets of the MHC peptide-binding groove. Bd-resistantLitoria verreauxii alpina(Livea-R), Bd-susceptible L. v.alpina (Livea-S), Bufogargarizans (Buga), Bombinaorientalis (Boor), Bombinabombina (Bobo), Bombinavariegata (Bova), Bombinapachypus (Bopa), Bufobufo (Bubu), Bufo[Epidalea] calamita(Buca), Rana [Lithobates]yavapaiensis (Raya),Rana [Lithobates]catesbeiana (Raca),susceptible Rana spp. (sRana)including Rana [Lithobates]clamitans, R. pipiens,R. [Lithobates]sylvatica, R.[Lithobates] warszewitschiiand Rana temporaria, Alytesobstetricans (Alob), Xenopuslaevis (Xela), Andriasdavidianus (Anda), Ambystomamexicanum and A. tigrinum(Anme/Amti). Raya-Q, allelefrom Rana [Lithobates]yavapaiensis associated withBd resistance. The complete alignment with allMHC-II β1 included in the study is available in theelectronic supplementary material.
Mentions: The MHC-II β1 alleles of amphibian species least affected by Bd infection[21–25] consistently presented thesame amino acids, or amino acids with similar chemical properties, at all 15pocket residues (figure 1 andtable 1; electronicsupplementary material, figure S1). By contrast, these pocket-specific aminoacid compositions were less frequent in species susceptible to Bd [19,20] (P4: , p = 0.009; P6:, p < 0.001; P9:, p = 0.04; table 1). Figure 1.

Bottom Line: We found that Bd-resistant amphibians across four continents share common amino acids in three binding pockets of the MHC-II antigen-binding groove.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Behavioral and Population Ecology, School of Biological Sciences, Seoul National University, Seoul 151-747, South Korea.

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.

Show MeSH
Related in: MedlinePlus