Open AccessIdentification of epitopes in ovalbumin that provide insights for cancer neoepitopes
Author(s) -
Sukrut Hemant Karandikar,
John Sidney,
Alessandro Sette,
Mark Selby,
Alan J. Korman,
Pramod K. Srivastava
Publication year - 2019
Publication title -
jci insight
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.099
H-Index - 45
ISSN - 2379-3708
DOI - 10.1172/jci.insight.127882
Subject(s) - epitope , ovalbumin , cd8 , biology , cytotoxic t cell , linear epitope , antigen , genetically modified mouse , microbiology and biotechnology , immunology , cancer research , in vitro , transgene , genetics , gene
MHC I-restricted epitopes of chicken ovalbumin (OVA) were originally identified using CD8 T cells as probes. Here, using bioinformatics tools, we identify four additional epitopes in OVA in addition to a cryptic epitope. Each new epitope is presented in vivo, as deduced from the lack of CD8 response to it in OVA-transgenic mice. In addition, CD8 responses to the known and novel epitopes are examined in C57BL/6 mice exposed to the OVA-expressing tumor E.G7 in several ways. No responses to any epitope including SIINFEKL are detected in mice with growing E.G7 or mice immunized with the tumor. Only in E.G7-bearing mice treated with an anti-CTLA4 antibody which depletes tumor-infiltrating regulatory T cells, CD8 responses to SIINFEKL and the novel epitope EKYNLTSVL are detected. Finally, all epitopes fails to treat mice with pre-existing tumors. These observations force an important re-consideration of the common assumptions about the therapeutic value of neoepitopes detected by CD8 responses in tumor-bearing hosts.