PMID- 29531227
OWN - NLM
STAT- MEDLINE
DCOM- 20180515
LR  - 20190312
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 9
IP  - 1
DP  - 2018 Mar 12
TI  - Divergent T-cell receptor recognition modes of a HLA-I restricted extended 
      tumour-associated peptide.
PG  - 1026
LID - 10.1038/s41467-018-03321-w [doi]
LID - 1026
AB  - Human leukocyte antigen (HLA)-I molecules generally bind short peptides (8-10 
      amino acids), although extended HLA-I restricted peptides (>10 amino acids) can 
      be presented to T cells. However, the function of such extended HLA-I epitopes in 
      tumour immunity, and how they would be recognised by T-cell receptors (TCR) 
      remains unclear. Here we show that the structures of two distinct TCRs 
      (TRAV4(+)TRAJ21(+)-TRBV28(+)TRBJ2-3(+) and TRAV4 (+) 
      TRAJ8(+)-TRBV9(+)TRBJ2-1(+)), originating from a polyclonal T-cell repertoire, 
      bind to HLA-B*07:02, presenting a 13-amino-acid-long tumour-associated peptide, 
      NY-ESO-1(60-72). Comparison of the structures reveals that the two TCRs 
      differentially binds NY-ESO-1(60-72)-HLA-B*07:02 complex, and induces differing 
      extent of conformational change of the NY-ESO-1(60-72) epitope. Accordingly, 
      polyclonal TCR usage towards an extended HLA-I restricted tumour epitope 
      translates to differing TCR recognition modes, whereby extensive flexibility at 
      the TCR-pHLA-I interface engenders recognition.
FAU - Chan, Kok Fei
AU  - Chan KF
AUID- ORCID: 0000-0001-7383-6544
AD  - Olivia Newton-John Cancer Research Institute, and School of Cancer Medicine, La 
      Trobe University, Heidelberg, VIC, 3084, Australia.
AD  - Department of Microbiology and Immunology, Peter Doherty Institute for Infection 
      and Immunity, The University of Melbourne, Parkville, VIC, 3010, Australia.
AD  - Infection and Immunity Program and Department of Biochemistry and Molecular 
      Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, 
      Australia.
AD  - Department of Biochemistry & Genetics, La Trobe Institute of Molecular Science, 
      La Trobe University, Bundoora, VIC, 3086, Australia.
FAU - Gully, Benjamin S
AU  - Gully BS
AD  - Infection and Immunity Program and Department of Biochemistry and Molecular 
      Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, 
      Australia.
AD  - Australian Research Council Centre of Excellence for Advanced Molecular Imaging, 
      Monash University, Clayton, VIC, 3800, Australia.
FAU - Gras, Stephanie
AU  - Gras S
AD  - Infection and Immunity Program and Department of Biochemistry and Molecular 
      Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, 
      Australia.
AD  - Australian Research Council Centre of Excellence for Advanced Molecular Imaging, 
      Monash University, Clayton, VIC, 3800, Australia.
FAU - Beringer, Dennis X
AU  - Beringer DX
AD  - Infection and Immunity Program and Department of Biochemistry and Molecular 
      Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, 
      Australia.
FAU - Kjer-Nielsen, Lars
AU  - Kjer-Nielsen L
AD  - Department of Microbiology and Immunology, Peter Doherty Institute for Infection 
      and Immunity, The University of Melbourne, Parkville, VIC, 3010, Australia.
FAU - Cebon, Jonathan
AU  - Cebon J
AD  - Olivia Newton-John Cancer Research Institute, and School of Cancer Medicine, La 
      Trobe University, Heidelberg, VIC, 3084, Australia.
FAU - McCluskey, James
AU  - McCluskey J
AUID- ORCID: 0000-0002-8597-815X
AD  - Department of Microbiology and Immunology, Peter Doherty Institute for Infection 
      and Immunity, The University of Melbourne, Parkville, VIC, 3010, Australia.
FAU - Chen, Weisan
AU  - Chen W
AUID- ORCID: 0000-0002-5221-9771
AD  - Olivia Newton-John Cancer Research Institute, and School of Cancer Medicine, La 
      Trobe University, Heidelberg, VIC, 3084, Australia. weisan.chen@latrobe.edu.au.
AD  - Department of Biochemistry & Genetics, La Trobe Institute of Molecular Science, 
      La Trobe University, Bundoora, VIC, 3086, Australia. weisan.chen@latrobe.edu.au.
FAU - Rossjohn, Jamie
AU  - Rossjohn J
AUID- ORCID: 0000-0002-2020-7522
AD  - Infection and Immunity Program and Department of Biochemistry and Molecular 
      Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, 3800, 
      Australia. jamie.rossjohn@monash.edu.
AD  - Australian Research Council Centre of Excellence for Advanced Molecular Imaging, 
      Monash University, Clayton, VIC, 3800, Australia. jamie.rossjohn@monash.edu.
AD  - Institute of Infection and Immunity, Cardiff University School of Medicine, Heath 
      Park, Cardiff, CF14 4XN, UK. jamie.rossjohn@monash.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20180312
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (HLA-B*07:02 antigen)
RN  - 0 (HLA-B7 Antigen)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Peptides)
RN  - 0 (Receptors, Antigen, T-Cell)
SB  - IM
MH  - HLA-B7 Antigen/chemistry/genetics/*metabolism
MH  - Humans
MH  - Models, Molecular
MH  - Neoplasm Proteins/chemistry/genetics/*metabolism
MH  - Neoplasms/genetics/*metabolism
MH  - Peptides/chemistry/genetics/*metabolism
MH  - Protein Binding
MH  - Receptors, Antigen, T-Cell/chemistry/genetics/*metabolism
PMC - PMC5847591
COIS- The authors declare no competing interests.
EDAT- 2018/03/14 06:00
MHDA- 2018/05/16 06:00
PMCR- 2018/03/12
CRDT- 2018/03/14 06:00
PHST- 2017/09/06 00:00 [received]
PHST- 2018/02/06 00:00 [accepted]
PHST- 2018/03/14 06:00 [entrez]
PHST- 2018/03/14 06:00 [pubmed]
PHST- 2018/05/16 06:00 [medline]
PHST- 2018/03/12 00:00 [pmc-release]
AID - 10.1038/s41467-018-03321-w [pii]
AID - 3321 [pii]
AID - 10.1038/s41467-018-03321-w [doi]
PST - epublish
SO  - Nat Commun. 2018 Mar 12;9(1):1026. doi: 10.1038/s41467-018-03321-w.