TY - JOUR
T1 - Use of HLA peptidomics and whole exome sequencing to identify human immunogenic neo-antigens
AU - Kalaora, Shelly
AU - Barnea, Eilon
AU - Merhavi-Shoham, Efrat
AU - Qutob, Nouar
AU - Teer, Jamie K.
AU - Shimony, Nilly
AU - Schachter, Jacob
AU - Rosenberg, Steven A.
AU - Besser, Michal J.
AU - Admon, Arie
AU - Samuels, Yardena
PY - 2016
Y1 - 2016
N2 - The antigenicity of cells is demarcated by the peptides bound by their Human Leucocyte Antigen (HLA) molecules. Through this antigen presentation, T cell specificity response is controlled. As a fraction of the expressed mutated peptides is presented on the HLA, these neo-epitopes could be immunogenic. Such neo-antigens have recently been identified through screening for predicted mutated peptides, using synthetic peptides or ones expressed from minigenes, combined with screening of patient tumor-infiltrating lymphocytes (TILs). Here we present a time and cost-effective method that combines whole-exome sequencing analysis with HLA peptidome mass spectrometry, to identify neo-antigens in a melanoma patient. Of the 1,019 amino acid changes identified through exome sequencing, two were confirmed by mass spectrometry to be presented by the cells. We then synthesized peptides and evaluated the two mutated neo-antigens for reactivity with autologous bulk TILs, and found that one yielded mutant-specific T-cell response. Our results demonstrate that this method can be used for immune response prediction and promise to provide an alternative approach for identifying immunogenic neo-epitopes in cancer.
AB - The antigenicity of cells is demarcated by the peptides bound by their Human Leucocyte Antigen (HLA) molecules. Through this antigen presentation, T cell specificity response is controlled. As a fraction of the expressed mutated peptides is presented on the HLA, these neo-epitopes could be immunogenic. Such neo-antigens have recently been identified through screening for predicted mutated peptides, using synthetic peptides or ones expressed from minigenes, combined with screening of patient tumor-infiltrating lymphocytes (TILs). Here we present a time and cost-effective method that combines whole-exome sequencing analysis with HLA peptidome mass spectrometry, to identify neo-antigens in a melanoma patient. Of the 1,019 amino acid changes identified through exome sequencing, two were confirmed by mass spectrometry to be presented by the cells. We then synthesized peptides and evaluated the two mutated neo-antigens for reactivity with autologous bulk TILs, and found that one yielded mutant-specific T-cell response. Our results demonstrate that this method can be used for immune response prediction and promise to provide an alternative approach for identifying immunogenic neo-epitopes in cancer.
KW - HLA
KW - TILs
UR - http://www.scopus.com/inward/record.url?scp=84958064376&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84958064376&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.6960
DO - 10.18632/oncotarget.6960
M3 - Article
C2 - 26819371
AN - SCOPUS:84958064376
SN - 1949-2553
VL - 7
SP - 5110
EP - 5117
JO - Oncotarget
JF - Oncotarget
IS - 5
ER -