T cell allorecognition via molecular mimicry
| Autor: | Fleur Elizabeth Tynan, Lars Kjer-Nielsen, Andrew G. Brooks, James McCluskey, John W. Kappler, Craig Steven Clements, Stephanie Gras, Scott R. Burrows, Anthony W. Purcell, Jamie Rossjohn, Matthew C.J. Wilce, Mandvi Bharadwaj, David C. Jackson, Frances Crawford, W.A. Macdonald, Julia K. Archbold, Philippa M. Saunders, Zhenjun Chen, Brian Stadinsky |
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| Rok vydání: | 2009 |
| Předmět: |
STRUCTURE
PROTEINS T cell T-Lymphocytes Immunology Antigen presentation Receptors Antigen T-Cell Human leukocyte antigen Biology medicine.disease_cause Lymphocyte Activation Transfection Cell Line HLA-B8 Antigen Jurkat Cells HLA-B Antigens medicine Immunology and Allergy Humans MOLIMMUNO Allorecognition T-cell receptor Molecular Mimicry MHC restriction Molecular biology Molecular mimicry Infectious Diseases medicine.anatomical_structure Epstein-Barr Virus Nuclear Antigens Peptides |
| Zdroj: | Immunity. 31(6) |
| ISSN: | 1097-4180 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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