The antigen presentation of MCMV specific Qa-1-restricted CD8 +T cells

Abstract

Abstract Murine cytomegalovirus (MCMV) is a well-established model system for human CMV (HCMV), a ubiquitous herpesvirus that affects over 70% of people worldwide. Although the classical CD8 +T cell response to MCMV has been well characterized, little is known about the non-classical CD8 +T cell response. Our laboratory recently demonstrated that Qa-1-restricted CD8 +T cells are sufficient to protect mice from MCMV induced lethality. Our recent data shows that this protective T cell population has limited αβ TCR diversity. To identify the MCMV peptide(s) presented by Qa-1, we utilized bioinformatic tools that predict MHC binding, including NetMHC 4.0 and T Cell Epitope Prediction tools available on the Immune Epitope Database and Analysis Resource. Using these tools, we queried the entire MCMV coding sequence to identify potential nonamers predicted to bind to Qa-1. Furthermore, these candidates were also queried to identify protease cleavage sites to ensure that they are predicted to exist in vivo. Approximately 40 potential peptides were selected and tested in an in vitroscreen using Qa-1 expressing cell lines. Our results suggest that several candidate peptides bind to Qa-1 as strongly as well-defined canonical binding partners. Taken together, these data suggest that an MCMV-responsive T cell population with limited αβ TCR diversity recognizes MCMV-derived peptides presented by Qa-1. This population is likely to be of importance for viral protection when classical CD8 +T cell immunity is compromised. This work is supported by the NIH Research Grant AI046709. Shanelle Reilly is supported by research supplement R01 3AI046709-18S1 to promote diversity.