Bats have been involved in transmission of highly contagious and deadly viruses to humans over the past five decades. Some proven examples of these viruses include SARS, Marburg, MERS, Nipah, Hendra, and Ebola. Despite carrying these viruses, bats themselves often remain asymptomatic, indicating that they have developed effective antiviral mechanisms over millions of years of coexistence with these and related viruses. While bat innate immunity has been widely investigated, progress in characterizing their adaptive immune system has been slow, largely due to a lack of specific reagents. However, our team has made major steps forward by providing insights into peptide antigen repertoires presented by different classes of bat MHC I. We have evidence that demonstrates there are 3- to 5- amino acid insertions in the bat MHC class I α1 domain that enables these molecules in P.alecto (black flying fox) to accommodate longer peptides, up to 15 amino acid residues in length. Motif analysis of endogenous peptides also revealed the selection of novel peptide sequences by bat MHC compared to humans. These findings highlight a possible crucial role of bat adaptive immune system, particularly cell-mediated response, in immune surveillance and defense against viral infections.
In the current study, we aimed to delve deeper into investigating the peptide repertoire presented by bat MHCI, molecular basis of peptide loading and antigen presentation, as well as the nature of the TCR-peptide-MHC complex, in P.alecto, with a specific focus on its response to emerging infectious diseases. To achieve these goals, we first generated, screened and successfully validated monoclonal antibodies against key molecules involved in bat cellular-mediated immunity, such as MHC I. These antibodies will be used in various applications to more effectively characterise cell mediated immunity in bats and to interrogate the specificity of this response at the molecular level. With this knowledge, we hope to develop effective anti-viral strategies to improve the quality of life for humans and livestock, and to prevent future pandemics.