Abstract
Mutations at codons 12, 13 or 61 of the ras proto-oncogenes are found in adenocarcinomas of the colon and rectum. Mutated ras encode tumor-specific proteins, and can elicit CD4+ HLA-class-II-restricted T cell responses both in mouse and man. The function of such T cells is, however, unclear. In a model system, we investigated whether HLA-class-II restricted CD4+ T cells, specific for a particular peptide derived from mutant p21 ras (Gln61-->Leu), might inhibit the growth of a colonic cancer cell line, when it was cultured in the presence of the corresponding peptide. We found in this case that the growth of the colonic adenocarcinoma cell line HT29, when also induced to express HLA class II molecules by interferon gamma treatment, was inhibited. The inhibition was peptide-specific and required the presence of HLA-DQ8 molecules on the target cell. However, HLA-DQ8-expressing HT29 cells functioned poorly as antigen-presenting cells and could only induce a weak proliferative T cell response in the presence of interleukin-2. The results suggest that colonic cancer cells expressing peptides derived from mutant p21 ras protein in a complex with HLA class II molecules may be a target for tumor-specific T cells. The results also indicate, however, that an initiation of the immune response will require "professional" antigen-presenting cells.