A K-ras 13Gly-->Asp mutation is recognized by HLA-DQ7 restricted T cells in a patient with colorectal cancer. Modifying effect of DQ7 on established cancers harbouring this mutation?

We have characterized and described in detail 2 CD4+ T-lymphocyte clones (TLC) from a colonic cancer patient. These TLC specifically recognize a K-ras-derived peptide carrying the 13Asp mutation commonly found in adenocarcinomas of the colon. The TLC were independently derived, as they carried 2 different T-cell receptors. The TLC recognized partly overlapping epitopes within the 13Asp peptide, presented by HLA-DQ7 molecules, suggesting that this molecule might confer some protective immunity against the mutation. On the basis of analysis of 251 colonic carcinomas, the presence of HLA-DQ7 did not seem to protect against the establishment of carcinomas carrying the 13Asp mutation, since the frequency of the DQ7 haplotype was not decreased among patients having this mutation. A modifying effect of DQ7 on the development of carcinomas with a 13Asp mutation was, however, observed, resulting in fewer tumours reaching advanced Dukes stages when DQ7 was present.