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Identification of a A naturally Processed HLA-A*02:01-Restricted CTL Epitope from the Human Tumor-Associated Antigen Nectin-4

Lopez et al., Cancer immunology, immunotherapy (2016) - PMID: 27514672

Product(s) used in this publication:  PepTrack™ Peptide Libraries

Abstract:

Nectin-4 is a tumor antigen present on the surface of breast, ovarian and lung carcinoma cells. It is rarely present in normal adult tissues and is therefore a candidate target for cancer immunotherapy. Here, we identified a Nectin-4 antigenic peptide that is naturally presented to T cells by HLA-A2 molecules. We first screened the 502 nonamer peptides of Nectin-4 (510 amino acids) for binding to and off-rate from eight different HLA class I molecules. We then combined biochemical, cellular and algorithmic assays to select 5 Nectin-4 peptides that bound to HLA-A*02:01 molecules. Cytolytic T lymphocytes were obtained from healthy donors, that specifically lyzed HLA-A2+ cells pulsed with 2 out of the 5 peptides, indicating the presence of anti-Nectin-4 CD8+ T lymphocytes in the human T cell repertoire. Finally, an HLA-A2-restricted cytolytic T cell clone derived from a breast cancer patient recognized peptide Nectin-4145-153 (VLVPPLPSL) and lyzed HLA-A2+Nectin-4+ breast carcinoma cells. These results indicate that peptide Nectin-4145-153 is naturally processed for recognition by T cells on HLA-A2 molecules. It could be used to monitor antitumor T cell responses or to immunize breast cancer patients.

KEYWORDS:

CTL; Epitope; MHC class I; Nectin-4; Tumor vaccine; Tumor-associated antigen

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