T Cell Allorecognition via Molecular Mimicry

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 extensiv...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2009-12, Vol.31 (6), p.897-908
Main Authors: Macdonald, Whitney A., Chen, Zhenjun, Gras, Stephanie, Archbold, Julia K., Tynan, Fleur E., Clements, Craig S., Bharadwaj, Mandvi, Kjer-Nielsen, Lars, Saunders, Philippa M., Wilce, Matthew C.J., Crawford, Fran, Stadinsky, Brian, Jackson, David, Brooks, Andrew G., Purcell, Anthony W., Kappler, John W., Burrows, Scott R., Rossjohn, Jamie, McCluskey, James
Format: Article
Language:English
Subjects:
Cell Line
Epstein-Barr Virus Nuclear Antigens - immunology
HLA-B Antigens - immunology
HLA-B8 Antigen
Humans
Jurkat Cells
Ligands
Lymphocyte Activation - immunology
Lymphocytes
Molecular Mimicry - immunology
MOLIMMUNO
Peptides
Peptides - chemistry
Peptides - immunology
PROTEINS
Receptors, Antigen, T-Cell - chemistry
Receptors, Antigen, T-Cell - immunology
Receptors, Antigen, T-Cell - metabolism
STRUCTURE
T cell receptors
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
Transfection
Transplants & implants
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Description
Summary: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.
ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2009.09.025