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 |
|---|---|
| Pages (from-to) | 21149-21158 |
| Number of pages | 10 |
| Journal | Journal of Biological Chemistry |
| Volume | 292 |
| Issue number | 51 |
| DOIs | |
| Publication status | Published - 22 Dec 2017 |
Cite this
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A conserved energetic footprint underpins recognition of human leukocyte antigen-E by two distinct αβ T cell receptors. / Sullivan, Lucy C.; Walpole, Nicholas G.; Farenc, Carine; Pietra, Gabriella ; Sum, Matthew J.W.; Clements, Craig S.; Lee, Eleanor J.; Beddoe, Travis; Falco, Michela; Mingari, Maria Cristina; Moretta, Lorenzo; Gras, Stephanie; Rossjohn, Jamie; Brooks, Andrew G.
In: Journal of Biological Chemistry, Vol. 292, No. 51, 22.12.2017, p. 21149-21158.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - A conserved energetic footprint underpins recognition of human leukocyte antigen-E by two distinct αβ T cell receptors
AU - Sullivan, Lucy C.
AU - Walpole, Nicholas G.
AU - Farenc, Carine
AU - Pietra, Gabriella
AU - Sum, Matthew J.W.
AU - Clements, Craig S.
AU - Lee, Eleanor J.
AU - Beddoe, Travis
AU - Falco, Michela
AU - Mingari, Maria Cristina
AU - Moretta, Lorenzo
AU - Gras, Stephanie
AU - Rossjohn, Jamie
AU - Brooks, Andrew G.
PY - 2017/12/22
Y1 - 2017/12/22
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85039433166&partnerID=8YFLogxK
U2 - 10.1074/jbc.M117.807719
DO - 10.1074/jbc.M117.807719
M3 - Article
VL - 292
SP - 21149
EP - 21158
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 1083-351X
IS - 51
ER -