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The Serpin-like Loop-insertion of Ovalbumin Increases Stability and Reduces OVA 323-339 Epitope Immunogenicity

ABSTRACT: Chicken ovalbumin (cOVA) has been studied for decades primarily due to the robust genetic and molecular resources that are available for experimental investigations. cOVA is a member of the serpin superfamily of proteins that function as protease inhibitors, although cOVA does not exhibit this activity. As a serpin, cOVA possesses a protease-sensitive reactive-center loop that lies adjacent to the OVA 323-339 CD4+ T-cell epitope. We took advantage of the previously described single-substitution-variant, OVA R339T, which can undergo the dramatic structural transition observed in serpins to study how changes in loop size and protein stability influences CD4+ T-cell priming in vivo. We observed that the OVA R339T loop-insertion increases stability and protease resistance, resulting in reduced CD4+ T-cell priming of the OVA 323-339 epitope in SJL mice. These findings have implications for the design of more effective vaccines for the treatment of infectious diseases and cancer as well as the development of more robust CD4+ T-cell-epitope prediction tools.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Gallus Gallus (chicken)

TISSUE(S): Macrophage

SUBMITTER: Daniel Moss

LAB HEAD: Samuel J. Landy

PROVIDER: PXD021756 | Pride | 2021-05-07

REPOSITORIES: Pride

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