Journal article
T Cell Allorecognition via Molecular Mimicry
WA Macdonald, Z Chen, S Gras, JK Archbold, FE Tynan, CS Clements, M Bharadwaj, L Kjer-Nielsen, PM Saunders, MCJ Wilce, F Crawford, B Stadinsky, D Jackson, AG Brooks, AW Purcell, JW Kappler, SR Burrows, J Rossjohn, J McCluskey
Immunity | CELL PRESS | Published : 2009
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-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 ..
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Funding Acknowledgements
We thank the staff at the GMCA-CAT beamline (Chicago, Advanced Photon Source) and the PX1 Beamline at the Australian synchrotron for assistance with data collection We thank Hugh Reid and Kim R Jordan for technical advice J R is a Federation Fellow of the Australian Research Council, C S C is an ARC QEII fellow, W A M is a Peter Doherty Postdoctoral Fellow, F E T is a CJ Martin Fellow, and A.W P, M C J W., and S R B are Senior Research Fellows of the National Health and Medical Research Council Australia This work was supported by grants from the ARC, NHMRC, and Roche Organ Transplant Research Foundation