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 (H ER-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 C TL. 19 synthetic peptides were evaluated for recognition by four HLA-A 2(+) 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 b y all four CTL lines. This peptide was specifically recognized by clon ed 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-2(high) ovarian tumor and a HER-2(high) 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 b y 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 m echanisms of tumor recognition by T cells, immunological tolerance to tumor, and structural characterization of tumor antigens.