T cell allorecognition via molecular mimicry

Immunity. 2009 Dec 18;31(6):897-908. doi: 10.1016/j.immuni.2009.09.025.


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 was associated with TCR specificity. Accordingly, molecular mimicry that is HLA and peptide dependent is a mechanism for human T cell alloreactivity between disparate cognate and allogeneic pHLA complexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Epstein-Barr Virus Nuclear Antigens / immunology*
  • HLA-B Antigens / immunology*
  • HLA-B8 Antigen
  • Humans
  • Jurkat Cells
  • Lymphocyte Activation / immunology
  • Molecular Mimicry / immunology*
  • Peptides / chemistry
  • Peptides / immunology
  • Receptors, Antigen, T-Cell / chemistry
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Transfection


  • EBNA-3A antigen
  • Epstein-Barr Virus Nuclear Antigens
  • HLA-B Antigens
  • HLA-B*08:01 antigen
  • HLA-B8 Antigen
  • Peptides
  • Receptors, Antigen, T-Cell

Associated data

  • PDB/3KPL
  • PDB/3KPM
  • PDB/3KPN
  • PDB/3KPO
  • PDB/3KPP
  • PDB/3KPQ
  • PDB/3KPR
  • PDB/3KPS