A conserved energetic footprint underpins recognition of human leukocyte antigen-E by two distinct αβ T cell receptors
Authors:
- 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.
Details:
Journal of Biological Chemistry, Volume 292, Issue 51, 2017-12-22
Article Link: Click here
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 CD8+ T cell 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. We report the structures of a TRBV9+ TCR in complex with the HLA-E molecule presenting the two peptides. Our data revealed that the TRBV9+ TCR adopts 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 into how monomorphic MHC molecules interact with T cells.