Recognition of a purified Mr-40,000 organ-specific immunogen of human lung cancer by class II-restricted T-cells.

An Mr-40,000 polypeptide (p40) was purified from a lung cancer cell line on the basis of its antigenicity with leukocytes from lung cancer patients in an in vitro immunological assay of leukocyte adherence inhibition. Here, the cells and mechanism responsible for recognizing the purified p40 organ-specific cancer neoantigen (OSN) were studied. Buffy coat leukocytes from lung cancer patients showed a bell-shaped dose response with a peak response at 0.75 micrograms/assay. Mononuclear cells showed a similar response pattern, whereas pure T-cells were unreactive. Monoclonal antibodies (MAbs) to T-cell differentiation antigens T3 and T4 inhibited the response in a dose-dependent fashion, whereas anti-T8 had no effect, indicating T helper cells and their T3-antigen receptor complex recognized the antigen. MAbs to class II major histocompatibility complex (MHC) antigens also inhibited the response, whereas MAbs to class I MHC had no effect, indicating an important role for class II MHC antigens of monocytes. None of the MAbs inhibited the response to OSN on membrane fragments, which is mediated by antibody-dependent monocytes. Trypsin- or cyanogen bromide-cleaved p40 OSN triggered a response at the same concentrations as the intact molecule. The p40 OSN incubated with live leukocytes showed less than 30% proteolytic digestion. The results indicate that class II-restricted T-cells recognize, via their antigen-specific cell surface receptors, contiguous sequences within the immunogenic tumor molecule in the context of the molecule or peptides binding to class II transplantation antigens.