A conserved energetic footprint underpins recognition of human leukocyte antigen-E by two distinct αß T cell receptors.
J Biol Chem
; 292(51): 21149-21158, 2017 12 22.
Article
in En
| MEDLINE
| ID: mdl-28972140
ABSTRACT
αß 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Histocompatibility Antigens Class I
/
Models, Molecular
/
Receptors, Antigen, T-Cell, alpha-beta
/
CD8-Positive T-Lymphocytes
/
Energy Metabolism
Limits:
Humans
Language:
En
Journal:
J Biol Chem
Year:
2017
Document type:
Article
Affiliation country:
Australia