作者
Smita S Chandran, Jiaqi Ma, Martin G Klatt, Friederike Dündar, Chaitanya Bandlamudi, Pedram Razavi, Hannah Y Wen, Britta Weigelt, Paul Zumbo, Si Ning Fu, Lauren B Banks, Fei Yi, Enric Vercher, Inaki Etxeberria, Watchain D Bestman, Arnaud Da Cruz Paula, Ilinca S Aricescu, Alexander Drilon, Doron Betel, David A Scheinberg, Brian M Baker, Christopher A Klebanoff
发表日期
2022/5
期刊
Nature medicine
卷号
28
期号
5
页码范围
946-957
出版商
Nature Publishing Group US
简介
Public neoantigens (NeoAgs) represent an elite class of shared cancer-specific epitopes derived from recurrently mutated driver genes. Here we describe a high-throughput platform combining single-cell transcriptomic and T cell receptor (TCR) sequencing to establish whether mutant PIK3CA, among the most frequently genomically altered driver oncogenes, generates an immunogenic public NeoAg. Using this strategy, we developed a panel of TCRs that recognize an endogenously processed neopeptide encompassing a common PIK3CA hotspot mutation restricted by the prevalent human leukocyte antigen (HLA)-A*03:01 allele. Mechanistically, immunogenicity to this public NeoAg arises from enhanced neopeptide/HLA complex stability caused by a preferred HLA anchor substitution. Structural studies indicated that the HLA-bound neopeptide presents a comparatively ‘featureless’ surface dominated by the …
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SS Chandran, J Ma, MG Klatt, F Dündar, C Bandlamudi… - Nature medicine, 2022