A mutated cyclin-dependent kinase 4 (CDK4) was identified as a tumor-specific 
antigen recognized by HLA-A2. 1-restricted autologous cytolytic T lymphocytes 
(CTLs) in a human melanoma. The mutated CDK4 allele was present in autologous 
cultured melanoma cells and metastasis tissue, but not in the patient's 
lymphocytes. The mutation, an arginine-to-cysteine exchange at residue 24, was 
part of the CDK4 peptide recognized by CTLs and prevented binding of the CDK4 
inhibitor p16INK4a, but not of p21 or of p27KIP1. The same mutation was found in 
one additional melanoma among 28 melanomas analyzed. These results suggest that 
mutation of CDK4 can create a tumor-specific antigen and can disrupt the 
cell-cycle regulation exerted by the tumor suppressor p16INK4a.