MHC class I loaded ligands from breast cancer cell lines: A potential HLA-I-typed antigen collection

Dmitri Rozanov, Nikita D. Rozanov, Kami E. Chiotti, Ashok Reddy, Phillip Wilmarth, Larry David, Seung W. Cha, Sunghee Woo, Pavel Pevzner, Vineet Bafna, Gregory G. Burrows, Juha K. Rantala, Trevor Levin, Pavana Anur, Katie Johnson-Camacho, Shaadi Tabatabaei, Daniel J. Munson, Tullia C. Bruno, Jill E. Slansky, John W. Kappler & 9 others Naoto Hirano, Sebastian Boegel, Bernard A. Fox, Colt Egelston, Diana L. Simons, Grecia Jimenez, Peter P. Lee, Joe Gray, Paul Spellman

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)13-23
Number of pages11
JournalJournal of Proteomics
Volume176
DOIs
StatePublished - Mar 30 2018

Fingerprint

Cells
Breast Neoplasms
Ligands
Cell Line
Peptides
I-antigen
Mutation
Epitopes
Tumor Escape
Subunit Vaccines
Immune system
Immunoprecipitation
Proteomics
Immune System
Neoplasms
Leukemia
Tumors
Vaccines
Genes
Throughput

Keywords

  • Breast cancer
  • MHC class I-restricted peptides
  • Neo-antigens
  • T cell-mediated immune response
  • Tumor associated antigens

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

Cite this

MHC class I loaded ligands from breast cancer cell lines : A potential HLA-I-typed antigen collection. / Rozanov, Dmitri; Rozanov, Nikita D.; Chiotti, Kami E.; Reddy, Ashok; Wilmarth, Phillip; David, Larry; Cha, Seung W.; Woo, Sunghee; Pevzner, Pavel; Bafna, Vineet; Burrows, Gregory G.; Rantala, Juha K.; Levin, Trevor; Anur, Pavana; Johnson-Camacho, Katie; Tabatabaei, Shaadi; Munson, Daniel J.; Bruno, Tullia C.; Slansky, Jill E.; Kappler, John W.; Hirano, Naoto; Boegel, Sebastian; Fox, Bernard A.; Egelston, Colt; Simons, Diana L.; Jimenez, Grecia; Lee, Peter P.; Gray, Joe; Spellman, Paul.

In: Journal of Proteomics, Vol. 176, 30.03.2018, p. 13-23.

Research output: Contribution to journalArticle

Rozanov, D, Rozanov, ND, Chiotti, KE, Reddy, A, Wilmarth, P, David, L, Cha, SW, Woo, S, Pevzner, P, Bafna, V, Burrows, GG, Rantala, JK, Levin, T, Anur, P, Johnson-Camacho, K, Tabatabaei, S, Munson, DJ, Bruno, TC, Slansky, JE, Kappler, JW, Hirano, N, Boegel, S, Fox, BA, Egelston, C, Simons, DL, Jimenez, G, Lee, PP, Gray, J & Spellman, P 2018, 'MHC class I loaded ligands from breast cancer cell lines: A potential HLA-I-typed antigen collection', Journal of Proteomics, vol. 176, pp. 13-23. https://doi.org/10.1016/j.jprot.2018.01.004
Rozanov, Dmitri ; Rozanov, Nikita D. ; Chiotti, Kami E. ; Reddy, Ashok ; Wilmarth, Phillip ; David, Larry ; Cha, Seung W. ; Woo, Sunghee ; Pevzner, Pavel ; Bafna, Vineet ; Burrows, Gregory G. ; Rantala, Juha K. ; Levin, Trevor ; Anur, Pavana ; Johnson-Camacho, Katie ; Tabatabaei, Shaadi ; Munson, Daniel J. ; Bruno, Tullia C. ; Slansky, Jill E. ; Kappler, John W. ; Hirano, Naoto ; Boegel, Sebastian ; Fox, Bernard A. ; Egelston, Colt ; Simons, Diana L. ; Jimenez, Grecia ; Lee, Peter P. ; Gray, Joe ; Spellman, Paul. / MHC class I loaded ligands from breast cancer cell lines : A potential HLA-I-typed antigen collection. In: Journal of Proteomics. 2018 ; Vol. 176. pp. 13-23.
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AU - Rozanov, Dmitri

AU - Rozanov, Nikita D.

AU - Chiotti, Kami E.

AU - Reddy, Ashok

AU - Wilmarth, Phillip

AU - David, Larry

AU - Cha, Seung W.

AU - Woo, Sunghee

AU - Pevzner, Pavel

AU - Bafna, Vineet

AU - Burrows, Gregory G.

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.

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