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Published on: February 28, 2019
The neoantigen quality model: Is closer to self more non-self?
Vinod P Balachandran1, Zachary Sethna2, Benjamin D Greenbaum3
1Immuno-Oncology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; David M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA; The Olayan Center for Cancer Vaccines, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Abstract:
T cells recognize antigens from pathogens and transformed cells. Yet what antigen is "ideal"? We propose a theoretical framework in which recognition is governed by T cell selection maximized near, not far from, self. Genomic errors generate antigens closer to self that paradoxically overlap with pathogen antigens and are immunogenic and non-self. We formalize this concept as the Neoantigen Quality Model, recasting antigen recognition as an adaptation to surveil the self and non-self living worlds.
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