Studying the gp100209 shared tumor antigen presented by HLA-A*02:01 (HLA-A2), we found that different TCRs distinguished between the identity of the side chain of the position 2 primary anchor residue: replacing the sub-optimal threonine at position 2 of the peptide with methionine weakened the binding of the gp100209/HLA-A2-specific TCR SILv44, but enhanced the binding of the gp100209/HLA-A2-specific TCR T4H2, despite no perceivable differences in the static crystallographic structures of the peptide/MHC complexes (5). This evidence concerns the gene HLA-C and neoplasm.