NetH2pan: A Computational Tool to Guide MHC Peptide Prediction on Murine Tumors.

Abstract:

:With the advancement of personalized cancer immunotherapies, new tools are needed to identify tumor antigens and evaluate T-cell responses in model systems, specifically those that exhibit clinically relevant tumor progression. Key transgenic mouse models of breast cancer are generated and maintained on the FVB genetic background, and one such model is the mouse mammary tumor virus-polyomavirus middle T antigen (MMTV-PyMT) mouse-an immunocompetent transgenic mouse that exhibits spontaneous mammary tumor development and metastasis with high penetrance. Backcrossing the MMTV-PyMT mouse from the FVB strain onto a C57BL/6 genetic background, in order to leverage well-developed C57BL/6 immunologic tools, results in delayed tumor development and variable metastatic phenotypes. Therefore, we initiated characterization of the FVB MHC class I H-2 q haplotype to establish useful immunologic tools for evaluating antigen specificity in the murine FVB strain. Our study provides the first detailed molecular and immunoproteomic characterization of the FVB H-2 q MHC class I alleles, including >8,500 unique peptide ligands, a multiallele murine MHC peptide prediction tool, and in vivo validation of these data using MMTV-PyMT primary tumors. This work allows researchers to rapidly predict H-2 peptide ligands for immune testing, including, but not limited to, the MMTV-PyMT model for metastatic breast cancer. Cancer Immunol Res; 6(6); 636-44. ©2018 AACR.

journal_name

Cancer Immunol Res

authors

DeVette CI,Andreatta M,Bardet W,Cate SJ,Jurtz VI,Jackson KW,Welm AL,Nielsen M,Hildebrand WH

doi

10.1158/2326-6066.CIR-17-0298

subject

Has Abstract

pub_date

2018-06-01 00:00:00

pages

636-644

issue

6

eissn

2326-6066

issn

2326-6074

pii

2326-6066.CIR-17-0298

journal_volume

6

pub_type

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