title: Characterization of the Antigen Processing Machinery and Endogenous Peptide Presentation of a Bat MHC Class I Molecule.
abstract: Bats are a major reservoir of emerging and re-emerging infectious diseases, including severe acute respiratory syndrome-like coronaviruses, henipaviruses, and Ebola virus. Although highly pathogenic to their spillover hosts, bats harbor these viruses, and a large number of other viruses, with little or no clinical signs of disease. How bats asymptomatically coexist with these viruses is unknown. In particular, little is known about bat adaptive immunity, and the presence of functional MHC molecules is mostly inferred from recently described genomes. In this study, we used an affinity purification/mass spectrometry approach to demonstrate that a bat MHC class I molecule, Ptal-N*01:01, binds antigenic peptides and associates with peptide-loading complex components. We identified several bat MHC class I-binding partners, including calnexin, calreticulin, protein disulfide isomerase A3, tapasin, TAP1, and TAP2. Additionally, endogenous peptide ligands isolated from Ptal-N*01:01 displayed a relatively broad length distribution and an unusual preference for a C-terminal proline residue. Finally, we demonstrate that this preference for C-terminal proline residues was observed in Hendra virus-derived peptides presented by Ptal-N*01:01 on the surface of infected cells. To our knowledge, this is the first study to identify endogenous and viral MHC class I ligands for any bat species and, as such, provides an important avenue for monitoring and development of vaccines against major bat-borne viruses both in the reservoir and spillover hosts. Additionally, it will provide a foundation to understand the role of adaptive immunity in bat antiviral responses.
authors.affiliation: CSIRO Health and Biosecurity, Australian Animal Health Laboratory, Geelong, Victoria 3220, Australia;
authors.forename: James W
authors.initials: JW
authors.lastname: Wynne
authors.affiliation: Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia; Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia; and.
authors.forename: Amanda P
authors.identifier: 0000-0002-4781-0356
authors.initials: AP
authors.lastname: Woon
authors.affiliation: Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia; Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia; and.
authors.forename: Nadine L
authors.initials: NL
authors.lastname: Dudek
authors.affiliation: Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia; Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia; and.
authors.forename: Nathan P
authors.identifier: 0000-0002-2128-5127
authors.initials: NP
authors.lastname: Croft
authors.affiliation: Program in Emerging Infectious Diseases, Duke-National University of Singapore Graduate Medical School, Singapore 169857, Republic of Singapore.
authors.forename: Justin H J
authors.identifier: 0000-0002-1076-6013
authors.initials: JH
authors.lastname: Ng
authors.affiliation: CSIRO Health and Biosecurity, Australian Animal Health Laboratory, Geelong, Victoria 3220, Australia;
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Baker
authors.affiliation: Program in Emerging Infectious Diseases, Duke-National University of Singapore Graduate Medical School, Singapore 169857, Republic of Singapore.
authors.forename: Lin-Fa
authors.initials: LF
authors.lastname: Wang
authors.affiliation: Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia; Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia; and anthony.purcell@monash.edu.
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Purcell
mesh_terms: D000483:Alleles; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology*; D000941:Antigens / Q000235:genetics / Q000276:immunology*; D002685:Chiroptera / Q000235:genetics / Q000276:immunology*; D005805:Genes, MHC Class I / Q000235:genetics / Q000276:immunology*; D006801:Humans; D010455:Peptides / Q000276:immunology*
chemical_list: D000941:Antigens; D010455:Peptides