IDENTIFICATION OF NATURALLY PROCESSED HUMAN OVARIAN PEPTIDES RECOGNIZED BY TUMOR-ASSOCIATED CD8(-LYMPHOCYTES() CYTOTOXIC T)

Identification of naturally processed peptides recognized by tumor-spe cific CTLs may lead to epitope-specific tumor vaccines, Because these epitopes may be expressed differently on epithelial tumors and may dif fer in their ability to induce CTL in vivo, we have isolated the HLA-A 2-peptide complexes by immunoaffinity from an established ovarian tumo r line transfected with and expressing HLA-AZ gene, High-performance l iquid chromatography-fractionated peptides were used to reconstitute e pitopes recognized on HLA-AZ by three HLA-A2(+) CD8(+) (3TL lines, The se lines recognized at least three of the same groups of fractions (de signated SKOV3.A, -B, and -C) but showed differences in the pattern of recognition of other fractions, To gain insight in the epitope distri bution by freshly isolated ovarian tumors, we compared the recognition of peaks SKOV3.B and -C with the corresponding peaks from an ovarian tumor (OVA-6) that expressed similar levels of HLA-AZ, using one of th ese lines (CTL-OVA-5) as indicator, CTL-OVA-5 recognized a large numbe r of epitopes from peaks B and C rechromatographed on more resolving h igh-performance liquid chromatography gradients, Although a number of peaks appeared to be coincident on both SKOV3 and OVA-6, an even highe r number appeared either not to overlap or to overlap only partially, These findings, which represent the first analysis of the epitopes pre sented by a patient tumor, suggest that the use of tumor line-derived peptides for vaccination may require selection of the epitopes corresp onding to the ones presented by freshly isolated human tumors.