A novel human HER2-derived peptide homologous to the mouse K(d)-restricted tumor rejection antigen can induce HLA-A24-restricted cytotoxic T lymphocytes in ovarian cancer patients and healthy individuals.
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| Abstract |
A mouse HER2-derived peptide, HER2p63 (A) (TYLPANASL), can induce K(d)-restricted mouse cytotoxic T lymphocytes (CTL) and also function as a tumor rejection antigen in an in vivo assay. Since the anchor motif of mouse K(d) for peptide binding has much similarity to that of human HLA-A2402, we asked if human HER2p63 (T) (TYLPTNASL) could induce HER2-specific CTL in HLA-A2402-positive individuals. Peripheral blood mononuclear cells (PBMC) of HLA-A2402-positive individuals were sensitized in vitro with HER2p63-pulsed autologous dendritic cells prepared from PBMC. CTL clone derived from these specifically lysed HER2-expressing cell lines bearing HLA-A2402. Cytotoxic activity of the CTL clone against the HER2-expressing cell line bearing HLA-A2402 was blocked by antibodies against CD3, CD8, HLA-A24 or MHC class I, and was also inhibited by the addition of excess HER2p63-pulsed C1R bearing HLA-A2402. Killer cells were generated from PBMC of seven healthy individuals and five ovarian cancer patients, all of HLA-A2402 type, by in vitro sensitization with HER2p63-pulsed autologous antigen presenting cells. These killer cells selectively lysed HER2-expressing SKOV3 transfected with HLA-A2402 cDNA, indicating high immunogenicity of HER2p63 in all 12 individuals examined.
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| Authors | T Okugawa, Y Ikuta, Y Takahashi, H Obata, K Tanida, M Watanabe, S Imai, R Furugen, Y Nagata, N Toyoda, H Shiku |
| Journal | European journal of immunology (Eur J Immunol) Vol. 30 Issue 11 Pg. 3338-46 (Nov 2000) ISSN: 0014-2980 [Print] Germany |
| PMID | 11093150 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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