Renal cell carcinoma-associated antigen G250 encodes a naturally processed epitope presented by human leukocyte antigen-DR molecules to CD4⁺ T lymphocytes

We previously identified an HLA-A2. I-restricted epitope within the RCC-associated antigen G250 that is recognized by CTLs. Using DCs of healthy individuals, which were loaded with overlapping 20 mer G250-derived peptides, we here report the induction of CD4⁺ T cells that recognize the G250 peptide of amino acids 249-268. Moreover, naturally processed G250 protein is readily recognized by these G250-specific CD4⁺ T cells in the context of HLA-DR molecules. Interestingly, peptide G250:249-268 overlaps the previously identified HLA-A2. I-restricted G250 epitope recognized by CTLs. These data and the high prevalence of G250 in RCC patients make peptide G250:249-268 a potential target in peptide-based vaccines to induce both CD4⁺ and CD8⁺ T-cell responses in patients.