T Cell Allorecognition via Molecular Mimicry

Macdonald, Whitney A., Chen, Zhenjun, Gras, Stephanie, Archbold, Julia K., Tynan, Fleur E., Clements, Craig S., Bharadwaj, Mandvi, Kjer-Nielsen, Lars, Saunders, Phillipa 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 and McCluskey, James (2009) T Cell Allorecognition via Molecular Mimicry. Immunity, 31 6: 897-908. doi:10.1016/j.immuni.2009.09.025

Author Macdonald, Whitney A.
Chen, Zhenjun
Gras, Stephanie
Archbold, Julia K.
Tynan, Fleur E.
Clements, Craig S.
Bharadwaj, Mandvi
Kjer-Nielsen, Lars
Saunders, Phillipa 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
Title T Cell Allorecognition via Molecular Mimicry
Journal name Immunity   Check publisher's open access policy
ISSN 1074-7613
Publication date 2009-12-18
Sub-type Article (original research)
DOI 10.1016/j.immuni.2009.09.025
Volume 31
Issue 6
Start page 897
End page 908
Total pages 12
Place of publication Cambridge, MA, United States
Publisher Cell Press
Language eng
Formatted abstract
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-B0801 bound to a viral peptide, alloreacts with B44 allotypes (HLA-B4402 and HLA-B4405) bound to two different allopeptides. Despite extensive polymorphism between HLA-B∗0801, HLA-B4402, and HLA-B4405 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-B4403, and the single residue polymorphism between HLA-B4402 and HLA-B4403 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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: ERA 2012 Admin Only
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Created: Tue, 25 Oct 2011, 09:40:00 EST by Geraldine Fitzgerald on behalf of School of Public Health