Open AccessThe Serpin-like Loop Insertion of Ovalbumin Increases the Stability and Decreases the OVA 323–339 Epitope Processing Efficiency
Author(s) -
Daniel L. Moss,
Ramgopal R. Mettu,
Samuel J. Landry
Publication year - 2021
Publication title -
biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.43
H-Index - 253
eISSN - 1520-4995
pISSN - 0006-2960
DOI - 10.1021/acs.biochem.1c00095
Subject(s) - serpin , epitope , ovalbumin , protease , proteases , chemistry , microbiology and biotechnology , biology , immune system , immunology , antibody , biochemistry , enzyme , gene
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 influence the processing and presentation of the OVA 323-339 epitope. We observed that the OVA R339T loop insertion increases the stability and protease resistance, resulting in the reduced presentation of the OVA 323-339 epitope in vitro . 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.