PMID- 23569211
OWN - NLM
STAT- MEDLINE
DCOM- 20130806
LR  - 20211021
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 288
IP  - 22
DP  - 2013 May 31
TI  - Highly divergent T-cell receptor binding modes underlie specific recognition of a 
      bulged viral peptide bound to a human leukocyte antigen class I molecule.
PG  - 15442-54
LID - 10.1074/jbc.M112.447185 [doi]
AB  - Human leukocyte antigen (HLA)-I molecules can present long peptides, yet the 
      mechanisms by which T-cell receptors (TCRs) recognize featured pHLA-I landscapes 
      are unclear. We compared the binding modes of three distinct human TCRs, CA5, 
      SB27, and SB47, complexed with a "super-bulged" viral peptide (LPEPLPQGQLTAY) 
      restricted by HLA-B*35:08. The CA5 and SB27 TCRs engaged HLA-B*35:08(LPEP) 
      similarly, straddling the central region of the peptide but making limited 
      contacts with HLA-B*35:08. Remarkably, the CA5 TCR did not contact the alpha1-helix 
      of HLA-B*35:08. Differences in the CDR3beta loop between the CA5 and SB27 TCRs 
      caused altered fine specificities. Surprisingly, the SB47 TCR engaged 
      HLA-B*35:08(LPEP) using a completely distinct binding mechanism, namely 
      "bypassing" the bulged peptide and making extensive contacts with the extreme 
      N-terminal end of HLA-B*35:08. This docking footprint included HLA-I residues not 
      observed previously as TCR contact sites. The three TCRs exhibited differing 
      patterns of alloreactivity toward closely related or distinct HLA-I allotypes. 
      Thus, the human T-cell repertoire comprises a range of TCRs that can interact 
      with "bulged" pHLA-I epitopes using unpredictable strategies, including the 
      adoption of atypical footprints on the MHC-I.
FAU - Liu, Yu Chih
AU  - Liu YC
AD  - Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, 
      Monash University, Clayton 3800, Australia.
FAU - Miles, John J
AU  - Miles JJ
FAU - Neller, Michelle A
AU  - Neller MA
FAU - Gostick, Emma
AU  - Gostick E
FAU - Price, David A
AU  - Price DA
FAU - Purcell, Anthony W
AU  - Purcell AW
FAU - McCluskey, James
AU  - McCluskey J
FAU - Burrows, Scott R
AU  - Burrows SR
FAU - Rossjohn, Jamie
AU  - Rossjohn J
FAU - Gras, Stephanie
AU  - Gras S
LA  - eng
SI  - PDB/4JRX
SI  - PDB/4JRY
GR  - 100326/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130408
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Complementarity Determining Regions)
RN  - 0 (HLA-B35 Antigen)
RN  - 0 (Peptides)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Viral Proteins)
SB  - IM
MH  - CD8-Positive T-Lymphocytes/cytology/*immunology
MH  - Complementarity Determining Regions/genetics/immunology
MH  - HLA-B35 Antigen/genetics/*immunology
MH  - Herpesvirus 4, Human/genetics/*immunology
MH  - Peptides/genetics/*immunology
MH  - Protein Structure, Secondary
MH  - Protein Structure, Tertiary
MH  - Receptors, Antigen, T-Cell/genetics/*immunology
MH  - Viral Proteins/genetics/*immunology
PMC - PMC3668706
OTO - NOTNLM
OT  - Major Histocompatibility Complex (MHC)
OT  - Structural Biology
OT  - T-cell Receptor
OT  - Viral Immunology
OT  - X-ray Crystallography
EDAT- 2013/04/10 06:00
MHDA- 2013/08/07 06:00
PMCR- 2013/04/08
CRDT- 2013/04/10 06:00
PHST- 2013/04/10 06:00 [entrez]
PHST- 2013/04/10 06:00 [pubmed]
PHST- 2013/08/07 06:00 [medline]
PHST- 2013/04/08 00:00 [pmc-release]
AID - S0021-9258(20)45936-8 [pii]
AID - M112.447185 [pii]
AID - 10.1074/jbc.M112.447185 [doi]
PST - ppublish
SO  - J Biol Chem. 2013 May 31;288(22):15442-54. doi: 10.1074/jbc.M112.447185. Epub 
      2013 Apr 8.