Abstract：
:The immune system can mount T cell responses against tumors; however, the antigen specificities of tumor-infiltrating lymphocytes (TILs) are not well understood. We used yeast-display libraries of peptide-human leukocyte antigen (pHLA) to screen for antigens of "orphan" T cell receptors (TCRs) expressed on TILs from human colorectal adenocarcinoma. Four TIL-derived TCRs exhibited strong selection for peptides presented in a highly diverse pHLA-A∗02:01 library. Three of the TIL TCRs were specific for non-mutated self-antigens, two of which were present in separate patient tumors, and shared specificity for a non-mutated self-antigen derived from U2AF2. These results show that the exposed recognition surface of MHC-bound peptides accessible to the TCR contains sufficient structural information to enable the reconstruction of sequences of peptide targets for pathogenic TCRs of unknown specificity. This finding underscores the surprising specificity of TCRs for their cognate antigens and enables the facile indentification of tumor antigens through unbiased screening.
journal_name
Celljournal_title
Cellauthors
Gee MH,Han A,Lofgren SM,Beausang JF,Mendoza JL,Birnbaum ME,Bethune MT,Fischer S,Yang X,Gomez-Eerland R,Bingham DB,Sibener LV,Fernandes RA,Velasco A,Baltimore D,Schumacher TN,Khatri P,Quake SR,Davis MM,Garcia KCdoi
10.1016/j.cell.2017.11.043subject
Has Abstractpub_date
2018-01-25 00:00:00pages
549-563.e16issue
3eissn
0092-8674issn
1097-4172pii
S0092-8674(17)31433-2journal_volume
172pub_type
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