PMID- 25505266
OWN - NLM
STAT- MEDLINE
DCOM- 20150415
LR  - 20210205
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 290
IP  - 5
DP  - 2015 Jan 30
TI  - Naturally processed non-canonical HLA-A*02:01 presented peptides.
PG  - 2593-603
LID - 10.1074/jbc.M114.607028 [doi]
AB  - Human leukocyte antigen (HLA) class I molecules generally present peptides (p) of 
      8 to 11 amino acids (aa) in length. Although an increasing number of examples 
      with lengthy (>11 aa) peptides, presented mostly by HLA-B alleles, have been 
      reported. Here we characterize HLA-A*02:01 restricted, in addition to the 
      HLA-B*0702 and HLA-B*4402 restricted, lengthy peptides (>11 aa) arising from the 
      B-cell ligandome. We analyzed a number of 15-mer peptides presented by 
      HLA-A*02:01, and confirmed pHLA-I formation by HLA folding and thermal stability 
      assays. Surprisingly the binding affinity and stability of the 15-mer epitopes in 
      complex with HLA-A*02:01 were comparable with the values observed for canonical 
      length (8 to 11 aa) HLA-A*02:01-restricted peptides. We solved the structures of 
      two 15-mer epitopes in complex with HLA-A*02:01, within which the peptides 
      adopted distinct super-bulged conformations. Moreover, we demonstrate that 
      T-cells can recognize the 15-mer peptides in the context of HLA-A*02:01, 
      indicating that these 15-mer peptides represent immunogenic ligands. 
      Collectively, our data expand our understanding of longer epitopes in the context 
      of HLA-I, highlighting that they are not limited to the HLA-B family, but can 
      bind the ubiquitous HLA-A*02:01 molecule, and play an important role in T-cell 
      immunity.
CI  - (c) 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
FAU - Hassan, Chopie
AU  - Hassan C
AD  - From the Departments of Immunohematology and Blood Transfusion and.
FAU - Chabrol, Eric
AU  - Chabrol E
AD  - the Department of Biochemistry and Molecular Biology, School of Biomedical 
      Sciences, Monash University, Clayton 3800, Australia.
FAU - Jahn, Lorenz
AU  - Jahn L
AD  - Hematology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
FAU - Kester, Michel G D
AU  - Kester MG
AD  - Hematology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
FAU - de Ru, Arnoud H
AU  - de Ru AH
AD  - From the Departments of Immunohematology and Blood Transfusion and.
FAU - Drijfhout, Jan W
AU  - Drijfhout JW
AD  - From the Departments of Immunohematology and Blood Transfusion and.
FAU - Rossjohn, Jamie
AU  - Rossjohn J
AD  - the Department of Biochemistry and Molecular Biology, School of Biomedical 
      Sciences, Monash University, Clayton 3800, Australia, the ARC Centre of 
      Excellence in Advanced Molecular Imaging, Monash University, Clayton 3800, 
      Australia, and the Institute of Infection and Immunity, Cardiff University School 
      of Medicine, Heath Park, Cardiff CF14 4XN, Wales, United Kingdom.
FAU - Falkenburg, J H Frederik
AU  - Falkenburg JH
AD  - Hematology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
FAU - Heemskerk, Mirjam H M
AU  - Heemskerk MH
AD  - Hematology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
FAU - Gras, Stephanie
AU  - Gras S
AD  - the Department of Biochemistry and Molecular Biology, School of Biomedical 
      Sciences, Monash University, Clayton 3800, Australia, the ARC Centre of 
      Excellence in Advanced Molecular Imaging, Monash University, Clayton 3800, 
      Australia, and stephanie.gras@monash.edu.
FAU - van Veelen, Peter A
AU  - van Veelen PA
AD  - From the Departments of Immunohematology and Blood Transfusion and 
      p.a.van_veelen@lumc.nl.
LA  - eng
SI  - PDB/4U6X
SI  - PDB/4U6Y
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141212
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-A*02:01 antigen)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (HLA-B*07:02 antigen)
RN  - 0 (HLA-B7 Antigen)
RN  - 0 (Peptides)
SB  - IM
MH  - Cell Line
MH  - Crystallography, X-Ray
MH  - Epitopes, T-Lymphocyte/chemistry/immunology
MH  - Flow Cytometry
MH  - HLA-A2 Antigen/*chemistry/immunology
MH  - HLA-B7 Antigen/chemistry/immunology
MH  - Humans
MH  - Mass Spectrometry
MH  - Peptides
MH  - Protein Conformation
PMC - PMC4317018
OTO - NOTNLM
OT  - Crystallography
OT  - HLA-A*02:01
OT  - Human Leukocyte Antigen Class I
OT  - Immunology
OT  - Mass Spectrometry (MS)
OT  - Peptide Conformation
OT  - Peptides
OT  - Peptidomics
OT  - T-cell Immunity
EDAT- 2014/12/17 06:00
MHDA- 2015/04/16 06:00
PMCR- 2016/01/30
CRDT- 2014/12/16 06:00
PHST- 2014/12/16 06:00 [entrez]
PHST- 2014/12/17 06:00 [pubmed]
PHST- 2015/04/16 06:00 [medline]
PHST- 2016/01/30 00:00 [pmc-release]
AID - S0021-9258(20)49237-3 [pii]
AID - M114.607028 [pii]
AID - 10.1074/jbc.M114.607028 [doi]
PST - ppublish
SO  - J Biol Chem. 2015 Jan 30;290(5):2593-603. doi: 10.1074/jbc.M114.607028. Epub 2014 
      Dec 12.