Abstract
αβ T cell receptors (TCRs) interact with peptides bound to the polymorphic major histocompatibility complex class Ia (MHC-Ia) and class II (MHC-II) molecules as well as the essentially monomorphic MHC class Ib (MHC-Ib) molecules. Although there is a large amount of information on how TCRs engage with MHC-Ia and MHC-II, our understanding of TCR/ MHC-Ib interactions is very limited. Infection with cytomegalovirus (CMV) can elicit a CD8Tcell response restricted by the human MHC-Ib molecule human leukocyte antigen (HLA)-E and specific for an epitope from UL40 (VMAPRTLIL), which is characterized by biased TRBV14 gene usage. Here we describe an HLA-E-restricted CD8+ T cell able to recognize an allotypic variant of the UL40 peptide with a modification at position 8 (P8) of the peptide (VMAPRTLVL) that uses the TRBV9 gene segment.Wereport the structures of aTRBV9TCRin complex with the HLA-E molecule presenting the two peptides. Our data revealed that the TRBV9+TCRadopts a different docking mode and molecular footprint atop HLA-E when compared with the TRBV14+ TCR-HLA-E ternary complex. Additionally, despite their differing V gene segment usage and different docking mechanisms, mutational analyses showed that the TCRs shared a conserved energetic footprint on the HLA-E molecule, focused around the peptide-binding groove. Hence, we provide new insights intohowmonomorphicMHCmolecules interact withT cells.
Original language | English |
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Pages (from-to) | 21149-21158 |
Number of pages | 10 |
Journal | The Journal of Biological Chemistry |
Volume | 292 |
Issue number | 51 |
DOIs | |
Publication status | Published - 22 Dec 2017 |
Equipment
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Australian Synchrotron
Office of the Vice-Provost (Research and Research Infrastructure)Facility/equipment: Facility
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Macromolecular Crystallisation Facility
Danuta Maksel (Manager)
Office of the Vice-Provost (Research and Research Infrastructure)Facility/equipment: Facility