A point mutation in the alpha-actinin-4 gene generates an antigenic peptide recognized by autologous cytolytic T lymphocytes on a human lung carcinoma

We have identified an antigen recognized on a human large cell carcinoma by an autologous tumor-specific CTL clone that was derived from mononuclear c ells infiltrating the primary tumor. The antigenic peptide is presented by HLA-A2 molecules and is encoded by the alpha -actinin-4 gene, which is expr essed ubiquitously. In the tumor cells, a point mutation generates an amino -acid change that is essential for recognition by the CTLs, The mutation wa s not found in alpha -actinin-4 cDNA sequences from about 50 lung carcinoma cell lines, suggesting that it is unique to this patient. Although he did not receive chemotherapy or radiotherapy, the patient has been without evid ence of tumor since the resection of the primary lesion in 1996, Using tetr amers of soluble HLA-A2 molecules loaded with the mutated antigenic peptide , anti-alpha -actinin-4 CTLs could be derived from blood samples collected from the patient in 1998 and 2000, It is possible that these CTLs, recogniz ing a truly tumor-specific antigen, play a role in the clinical evolution o f this lung cancer patient.