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T cells often alloreact with foreign human leukocyte antigens (HLA). Here we showed the LC13 T cell receptor (TCR), selected for recognition on self-HLA-B^∗0801 bound to a viral peptide, alloreacts with B44 allotypes (HLA-B^∗4402 and HLA-B^∗4405) bound to two different allopeptides. Despite extensive polymorphism between HLA-B^∗0801, HLA-B^∗4402, and HLA-B^∗4405 and the disparate sequences of the viral and allopeptides, the LC13 TCR engaged these peptide-HLA (pHLA) complexes identically, accommodating mimicry of the viral peptide by the allopeptide. The viral and allopeptides adopted similar conformations only after TCR ligation, revealing an induced-fit mechanism of molecular mimicry. The LC13 T cells did not alloreact against HLA-B^∗4403, and the single residue polymorphism between HLA-B^∗4402 and HLA-B^∗4403 affected the plasticity of the allopeptide, revealing that molecular mimicry …