The anti-influenza CD8⁺ T cell response in HLA-A2–positive adults is almost exclusively directed at residues 58–66 of the virus matrix protein (MP(58–66)). V_β17V_α10.2 T cell receptors (TCRs) containing a conserved arginine-serine-serine sequence in complementarity determining region 3 (CDR3) of the V_β segment dominate this response. To investigate the molecular basis of immunodominant selection in an outbred population, we have determined the crystal structure of V_β17V_α10.2 in complex with MP(58–66)–HLA-A2 at a resolution of 1.4 Å. We show that, whereas the TCR typically fits over an exposed side chain of the peptide, in this structure MP(58–66) exposes only main chain atoms. This distinctive orientation of V_β17V_α10.2, which is almost orthogonal to the peptide-binding groove of HLA-A2, facilitates insertion of the conserved arginine in V_β CDR3 into a notch in the surface of MP(58–66)–HLA-A2. This previously unknown binding mode underlies the immunodominant T cell response.