Cytotoxic T-lymphocytes (CTLs) specific for autologous human
squamous cell cancer of the lung were generated by stimulation of peripheral blood lymphocytes with autologous
tumor cells in vitro. The CTL line was >97% CD3+, CD8+, CD16- and produced
tumor necrosis factor-alpha,
gamma-interferon, and
granulocyte-macrophage colony-stimulating factor after stimulation with autologous
tumor. The CTLs lysed autologous
tumor but failed to recognize autologous or histocompatibility leukocyte
antigen-matched lymphoid cells, K562, or allogeneic
tumor cells of several histological types. Antibody-blocking studies suggested that the CTLs recognized one or more
antigens presented by the class I major histocompatibility complex molecule Aw68. To characterize these
antigens further, histocompatibility leukocyte
antigen Aw68 molecules were extracted from the
squamous cell cancer of the lung
tumor line by immunoaffinity chromatography, and the associated
peptides were eluted in
acid and separated by reversed-phase high-performance liquid chromatography. Reconstitution of the CTL
epitope was evaluated by adding these
peptides to autologous Epstein-Barr virus-transformed B-cells. Two peaks of reconstituting activity were observed, suggesting that these CTLs recognize at least two Aw68-associated
peptides. This study confirms the existence of a CTL response against autologous human
squamous cell cancer of the lung and suggests that this CTL response is directed against
peptide epitopes presented by the class I major histocompatibility complex molecules. It is anticipated that this approach will permit identification of
peptide epitopes for
lung cancer-specific CTLs.