Identification of an immunodominant peptide of HER-2/neu protooncogene recognized by ovarian tumor-specific cytotoxic T lymphocyte lines.
Synthetic peptide analogues of sequences in the HER-2 protooncogene (HER-2) were selected based on the presence of HLA-A2.1 anchor motifs to identify the epitopes on HER-2 recognized by ovarian tumor-reactive CTL. 19 synthetic peptides were evaluated for recognition by four HLA-A2 ovarian-specific cytotoxic T lymphocyte (CTL) lines obtained from leukocytes associated with ovarian tumors. The nonapeptide E75 (HER-2, 369-377:KIFGSLAFL) was efficient in sensitizing T2 cells for lysis by all four CTL lines. This peptide was specifically recognized by cloned CD8+ CTL isolated from one of the ovarian-specific CTL lines. E75-pulsed T2 cells inhibited lysis by the same CTL clone of both an HLA-A2+ HER-2high ovarian tumor and a HER-2high cloned ovarian tumor line transfected with HLA-A2, suggesting that this or a structurally similar epitope may be specifically recognized by these CTL on ovarian tumors. Several other HER-2 peptides were recognized preferentially by one or two CTL lines, suggesting that both common and private HER-2 epitopes may be immunogenic in patients with ovarian tumors. Since HER-2 is a self-antigen, these peptides may be useful for understanding mechanisms of tumor recognition by T cells, immunological tolerance to tumor, and structural characterization of tumor antigens.
Fisk
B
B
Department of Gynecologic Oncology, University of Texas, M.D. Anderson Cancer Center, Houston 77030, USA.
Blevins
T L
TL
Wharton
J T
JT
Ioannides
C G
CG
D000595:Amino Acid Sequence; D002460:Cell Line; D000939:Epitopes / Q000096:biosynthesis / Q000737:chemistry; D005260:Female; D018734:Genes, erbB-2; D015789:HLA-A2 Antigen / Q000096:biosynthesis; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology*; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D011519:Proto-Oncogenes; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000939:Epitopes; D015789:HLA-A2 Antigen; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases; D011994:Recombinant Proteins