Despite the growing number of studies showing an important role of CD4+ T cells in cancer [81], the data available on how their TCRs can recognise tumour antigens is limited to two TCRs (E8 and G4 [24,25]) recognising the same human melanoma epitope from the glycolytic enzyme triosephosphate isomerase presented by HLA-DR1 (TPI, Table 1). The gene discussed is TPI1; the disease is melanoma.