Identification of class I MHC-associated phosphopeptides as targets for cancer immunotherapy - PubMed (original) (raw)
Identification of class I MHC-associated phosphopeptides as targets for cancer immunotherapy
Angela L Zarling et al. Proc Natl Acad Sci U S A. 2006.
Abstract
Alterations in phosphorylation of cellular proteins are a hallmark of malignant transformation. Degradation of these phosphoproteins could generate cancer-specific class I MHC-associated phosphopeptides recognizable by CD8+ T lymphocytes. In a comparative analysis of phosphopeptides presented on the surface of melanoma, ovarian carcinoma, and B lymphoblastoid cells, we find 5 of 36 that are restricted to the solid tumors and common to both cancers. Differential presentation of these peptides can result from differential phosphorylation of the source proteins. Recognition of the peptides on cancer cells by phosphopeptide-specific CD8+ T lymphocytes validates the potential of these phosphopeptides as immunotherapeutic targets.
Conflict of interest statement
The authors declare no conflict of interest.
Figures
Fig. 1.
Differential phosphorylation of source proteins in cancer cells results in differential presentation of phosphorylated peptides by class I MHC. Shown are immunoblotting data for the expression of total IRS2 protein, phosphorylated IRS2 on Ser1100, total β-catenin, and phosphorylated β-catenin on Ser33. All blots were performed on 60 μg of protein, except in the case of the 2X JY BLCL, for which 120 μg of protein was probed. These results are representative of three independent experiments.
Fig. 2.
pIRS21097–1105-, pβ-catenin30–39-, and pCDC25b38–46-specific CD8+ T lymphocytes recognize endogenously processed and presented phosphopeptides on the surface of cancer cell lines. (A) Recognition of C1RAAD stimulators pulsed with the indicated concentrations of synthetic phosphopeptide or its nonphosphorylated homolog by either pIRS21097–1105- or pCDC25b38–46-specific CD8+ T lymphocytes (Left) or pβ-catenin30–39-specific CD8+ T lymphocytes (Right). (B) Recognition of endogenously processed phosphopeptides on the indicated cell lines by pIRS21097–1105-, pβ-catenin30–39-, and pCDC25b38–46-specific CD8+ T cells.
Comment in
- Tumors reveal their secrets to cytotoxic T cells.
Williamson NA, Rossjohn J, Purcell AW. Williamson NA, et al. Proc Natl Acad Sci U S A. 2006 Oct 3;103(40):14649-50. doi: 10.1073/pnas.0606951103. Epub 2006 Sep 27. Proc Natl Acad Sci U S A. 2006. PMID: 17005729 Free PMC article. No abstract available.
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References
- Rock KL, Goldberg AL. Annu Rev Immunol. 1999;17:739–779. - PubMed
- Harper JW. Trends Cell Biol. 2002;12:104–107. - PubMed
- Reed SI. Nat Rev Mol Cell Biol. 2003;4:855–864. - PubMed
- Koepp DM, Harper JW, Elledge SJ. Cell. 1999;97:431–434. - PubMed
- Ang XL, Wade Harper J. Oncogene. 2005;24:2860–2870. - PubMed
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