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?

Abstract

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.

• Authors: B Fossum, J Breivik, G I Meling, T Gedde-Dahl 3rd, T Hansen, I Knutsen, T O Rognum, E Thorsby, G Gaudernack
• Journal: International journal of cancer (Int J Cancer) Vol. 58 Issue 4 Pg. 506-11 (Aug 15 1994) ISSN: 0020-7136 [Print] United States
• PMID: 7914513 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• HLA-DQ Antigens

Topics

• Amino Acid Sequence
• CD4-Positive T-Lymphocytes (immunology)
• Colorectal Neoplasms (genetics)
• Conserved Sequence
• Female
• Genes, ras
• HLA-DQ Antigens
• Humans
• Middle Aged
• Molecular Sequence Data
• Mutation