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.

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.

journal_name

Eur J Immunol

authors

Okugawa T,Ikuta Y,Takahashi Y,Obata H,Tanida K,Watanabe M,Imai S,Furugen R,Nagata Y,Toyoda N,Shiku H

doi

10.1002/1521-4141(200011)30:11<3338::AID-IMMU3338>

keywords:

subject

Has Abstract

pub_date

2000-11-01 00:00:00

pages

3338-46

issue

11

eissn

0014-2980

issn

1521-4141

pii

10.1002/1521-4141(200011)30:11<3338::AID-IMMU3338>

journal_volume

30

pub_type

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