Single chain MHC-I-β2 microglobulin-peptide trimer constructs identify CD8 T cells recognizing low-affinity MHC-I-binding neoepitopes 

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Presentation Time: 05:00 PM - 05:15 PM
Abstract ID: 5506 - B

Presenting Author:
Stabonia Maji , Biomedical Sciences PhD student at UConn Hlth.

Abstract:

Cancer-specific neoepitopes (mutated peptides in tumor cells presented by MHC-I) are under intense scrutiny to understand the anti-tumor CD8 T cell response. Only a small minority of such potential neoepitopes actually elicit tumor control in vivo. A majority of the neoepitopes, that do mediate tumor control in vivo, have very low affinity for MHC-I, ranging from IC50 values between 500 nM and 50,000 nM (Duan et al., 2014; Brennick and George et al., 2021; Ebrahimi-Nik et al., 2021). This contrasts with the strong MHCI-binding (IC50 <100 nM) epitopes of viruses and model antigens (Peters et al., 2020). As expected, we have found it impossible to create MHC-I-tetramers for low-affinity tumor-controlling neoepitopes. Here, we have genetically created single chain trimers that contain MHC-I alleles, β2 microglobulin as well as the low-affinity peptide, for each of the nine low-affinity neoepitopes identified previously in our laboratory (Brennick and George et al., 2021). Such trimers have been purified and characterized and have been used to identify, for the first time, CD8 T cells that recognize low-affinity cancer neoepitopes presented by tumor MHC-I molecules. The characteristics (abundance, amplification, specificity etc) of these low-affinity MHC-I binding neoepitopes shall be presented.