Identification of a cyclin B1-derived CTL epitope eliciting spontaneous responses in both cancer patients and healthy donors.

Abstract

With the aim to identify cyclin B1-derived peptides with high affinity for HLA-A2, we used three in silico prediction algorithms to screen the protein sequence for possible HLA-A2 binders. One peptide scored highest in all three algorithms, and the high HLA-A2-binding affinity of this peptide was verified in an HLA stabilization assay. By stimulation with peptide-loaded dendritic cells a CTL clone was established, which was able to kill two breast cancer cell lines in an HLA-A2-dependent and peptide-specific manner, demonstrating presentation of the peptide on the surface of cancer cells. Furthermore, blood from cancer patients and healthy donors was screened for spontaneous T-cell reactivity against the peptide in IFN-γ ELISPOT assays. Patients with breast cancer, malignant melanoma, or renal cell carcinoma hosted powerful and high-frequency T-cell responses against the peptide. In addition, when blood from healthy donors was tested, similar responses were observed. Ultimately, serum from cancer patients and healthy donors was analyzed for anti-cyclin B1 antibodies. Humoral responses against cyclin B1 were frequently detected in both cancer patients and healthy donors. In conclusion, a high-affinity cyclin B1-derived HLA-A2-restricted CTL epitope was identified, which was presented on the cell surface of cancer cells, and elicited spontaneous T-cell responses in cancer patients and healthy donors.

• Authors: Rikke Sick Andersen, Rikke Bæk Sørensen, Cathrin Ritter, Inge Marie Svane, Jürgen C Becker, Per thor Straten, Mads Hald Andersen
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 60 Issue 2 Pg. 227-34 (Feb 2011) ISSN: 1432-0851 [Electronic] Germany
• PMID: 20981424 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies
• CCNB1 protein, human
• Cyclin B1
• Epitopes, T-Lymphocyte
• HLA-A2 Antigen

Topics

• Adult
• Aged
• Aged, 80 and over
• Algorithms
• Antibodies (blood, immunology)
• Cells, Cultured
• Cyclin B1 (chemistry, immunology)
• Enzyme-Linked Immunosorbent Assay
• Epitopes, T-Lymphocyte (immunology)
• HLA-A2 Antigen (immunology)
• Health
• Humans
• Middle Aged
• Neoplasms (blood, immunology)
• T-Lymphocytes, Cytotoxic (immunology)