Cell, Год журнала: 2017, Номер 172(3), С. 549 - 563.e16

Опубликована: Дек. 21, 2017

Highlights•Development of a human leukocyte antigen library for TCR ligand identification•Single-cell sequencing and phenotyping T cells infiltrating colon cancer•Ligand discovery four tumor-derived cell receptors•Identification shared non-mutated tumor between two patientsSummaryThe immune system can mount responses against tumors; however, the specificities tumor-infiltrating lymphocytes (TILs) are not well understood. We used yeast-display libraries peptide-human (pHLA) to screen antigens "orphan" receptors (TCRs) expressed on TILs from colorectal adenocarcinoma. Four TIL-derived TCRs exhibited strong selection peptides presented in highly diverse pHLA-A∗02:01 library. Three TIL were specific self-antigens, which present separate patient tumors, specificity self-antigen derived U2AF2. These results show that exposed recognition surface MHC-bound accessible contains sufficient structural information enable reconstruction sequences peptide targets pathogenic unknown specificity. This finding underscores surprising their cognate enables facile indentification through unbiased screening.Graphical abstract

Язык: Английский