TY - JOUR
T1 - MHC class I loaded ligands from breast cancer cell lines
T2 - A potential HLA-I-typed antigen collection
AU - Rozanov, Dmitri
AU - Rozanov, Nikita D.
AU - Chiotti, Kami E.
AU - Reddy, Ashok
AU - Wilmarth, Phillip A.
AU - David, Larry L.
AU - Cha, Seung W.
AU - Woo, Sunghee
AU - Pevzner, Pavel
AU - Bafna, Vineet
AU - Burrows, Gregory
AU - Rantala, Juha K.
AU - Levin, Trevor
AU - Anur, Pavana
AU - Johnson-Camacho, Katie
AU - Tabatabaei, Shaadi
AU - Munson, Daniel J.
AU - Bruno, Tullia C.
AU - Slansky, Jill E.
AU - Kappler, John W.
AU - Hirano, Naoto
AU - Boegel, Sebastian
AU - Fox, Bernard A.
AU - Egelston, Colt
AU - Simons, Diana L.
AU - Jimenez, Grecia
AU - Lee, Peter P.
AU - Gray, Joe W.
AU - Spellman, Paul T.
N1 - Publisher Copyright:
© 2018 The Authors
PY - 2018/3/30
Y1 - 2018/3/30
N2 - To build a catalog of peptides presented by breast cancer cells, we undertook systematic MHC class I immunoprecipitation followed by elution of MHC class I-loaded peptides in breast cancer cells. We determined the sequence of 3196 MHC class I ligands representing 1921 proteins from a panel of 20 breast cancer cell lines. After removing duplicate peptides, i.e., the same peptide eluted from more than one cell line, the total number of unique peptides was 2740. Of the unique peptides eluted, more than 1750 had been previously identified, and of these, sixteen have been shown to be immunogenic. Importantly, half of these immunogenic peptides were shared between different breast cancer cell lines. MHC class I binding probability was used to plot the distribution of the eluted peptides in accordance with the binding score for each breast cancer cell line. We also determined that the tested breast cancer cells presented 89 mutation-containing peptides and peptides derived from aberrantly translated genes, 7 of which were shared between four or two different cell lines. Overall, the high throughput identification of MHC class I-loaded peptides is an effective strategy for systematic characterization of cancer peptides, and could be employed for design of multi-peptide anticancer vaccines. Significance: By employing proteomic analyses of eluted peptides from breast cancer cells, the current study has built an initial HLA-I-typed antigen collection for breast cancer research. It was also determined that immunogenic epitopes can be identified using established cell lines and that shared immunogenic peptides can be found in different cancer types such as breast cancer and leukemia. Importantly, out of 3196 eluted peptides that included duplicate peptides in different cells 89 peptides either contained mutation in their sequence or were derived from aberrant translation suggesting that mutation-containing epitopes are on the order of 2–3% in breast cancer cells. Finally, our results suggest that interfering with MHC class I function is one of the mechanisms of how tumor cells escape immune system attack.
AB - To build a catalog of peptides presented by breast cancer cells, we undertook systematic MHC class I immunoprecipitation followed by elution of MHC class I-loaded peptides in breast cancer cells. We determined the sequence of 3196 MHC class I ligands representing 1921 proteins from a panel of 20 breast cancer cell lines. After removing duplicate peptides, i.e., the same peptide eluted from more than one cell line, the total number of unique peptides was 2740. Of the unique peptides eluted, more than 1750 had been previously identified, and of these, sixteen have been shown to be immunogenic. Importantly, half of these immunogenic peptides were shared between different breast cancer cell lines. MHC class I binding probability was used to plot the distribution of the eluted peptides in accordance with the binding score for each breast cancer cell line. We also determined that the tested breast cancer cells presented 89 mutation-containing peptides and peptides derived from aberrantly translated genes, 7 of which were shared between four or two different cell lines. Overall, the high throughput identification of MHC class I-loaded peptides is an effective strategy for systematic characterization of cancer peptides, and could be employed for design of multi-peptide anticancer vaccines. Significance: By employing proteomic analyses of eluted peptides from breast cancer cells, the current study has built an initial HLA-I-typed antigen collection for breast cancer research. It was also determined that immunogenic epitopes can be identified using established cell lines and that shared immunogenic peptides can be found in different cancer types such as breast cancer and leukemia. Importantly, out of 3196 eluted peptides that included duplicate peptides in different cells 89 peptides either contained mutation in their sequence or were derived from aberrant translation suggesting that mutation-containing epitopes are on the order of 2–3% in breast cancer cells. Finally, our results suggest that interfering with MHC class I function is one of the mechanisms of how tumor cells escape immune system attack.
KW - Breast cancer
KW - MHC class I-restricted peptides
KW - Neo-antigens
KW - T cell-mediated immune response
KW - Tumor associated antigens
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UR - http://www.scopus.com/inward/citedby.url?scp=85041571104&partnerID=8YFLogxK
U2 - 10.1016/j.jprot.2018.01.004
DO - 10.1016/j.jprot.2018.01.004
M3 - Article
C2 - 29331515
AN - SCOPUS:85041571104
SN - 1874-3919
VL - 176
SP - 13
EP - 23
JO - Journal of Proteomics
JF - Journal of Proteomics
ER -