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 HARBORING THIS MUTATION

We have characterized and described in detail 2 CD4(+) T-lymphocyte cl ones (TLC) from a colonic cancer patient. These TLC specifically recog nize a K-ras-derived peptide carrying the 13Asp mutation commonly foun d in adenocarcinomas of the colon. The TLC were independently derived, as they carried 2 different T-cell receptors. The TLC recognized part ly 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 coloni c 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 havin g this mutation. A modifying effect of DQ7 on the development of carci nomas with a 13Asp mutation was, however, observed, resulting in fewer tumours reaching advanced Dukes stages when DQ7 was present. (C) 1994 Wiley-Liss, Inc.