Related Experiment Video
Updated: Mar 21, 2026
Stability and Structure of Bat Major Histocompatibility Complex Class I with Heterologous β2-Microglobulin
Published on: March 10, 2021
Characterization of the Antigen Processing Machinery and Endogenous Peptide Presentation of a Bat MHC Class I
James W Wynne1, Amanda P Woon2, Nadine L Dudek2
1CSIRO Health and Biosecurity, Australian Animal Health Laboratory, Geelong, Victoria 3220, Australia;
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.
Insights
Bats asymptomatically carry viruses due to unique adaptive immunity. This study identifies bat MHC class I ligands, crucial for understanding viral coexistence and developing vaccines against bat-borne diseases.
Area of Science:
- Immunology
- Virology
- Mammalian Genetics
Background:
- Bats are reservoirs for numerous emerging infectious diseases, including coronaviruses, henipaviruses, and Ebola virus.
- The mechanisms by which bats asymptomatically harbor these viruses, particularly concerning their adaptive immunity, remain largely unknown.
- Functional major histocompatibility complex (MHC) molecules in bats are primarily inferred from genomic data.
Purpose of the Study:
- To investigate the function of bat MHC class I molecules in binding peptides.
- To identify specific MHC class I-binding partners and endogenous peptide ligands in bats.
- To understand the role of bat adaptive immunity in asymptomatic viral persistence.
Main Methods:
- Affinity purification coupled with mass spectrometry was employed to analyze bat MHC class I molecule interactions.
- Bat MHC class I molecule Ptal-N*01:01 was purified and its associated proteins and peptide ligands were identified.
- Infected cells were used to analyze viral peptides presented by Ptal-N*01:01.
Main Results:
- Bat MHC class I molecule Ptal-N*01:01 was confirmed to bind antigenic peptides and associate with peptide-loading complex components.
- Key MHC class I-binding partners, including calnexin, calreticulin, tapasin, TAP1, and TAP2, were identified.
- Endogenous peptide ligands from Ptal-N*01:01 showed a preference for C-terminal proline residues, a characteristic also observed in Hendra virus-derived peptides.
Conclusions:
- This study provides the first identification of endogenous and viral MHC class I ligands for any bat species.
- The findings offer a foundation for monitoring bat-borne viruses and developing vaccines for both reservoir and spillover hosts.
- Understanding bat adaptive immunity is critical for deciphering asymptomatic viral coexistence and antiviral responses.
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