PMID- 28855257
OWN - NLM
STAT- MEDLINE
DCOM- 20171026
LR  - 20210205
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 292
IP  - 42
DP  - 2017 Oct 20
TI  - The molecular basis for peptide repertoire selection in the human leucocyte 
      antigen (HLA) C*06:02 molecule.
PG  - 17203-17215
LID - 10.1074/jbc.M117.806976 [doi]
AB  - Human leukocyte antigen (HLA)-C*06:02 is identified as the allele associated with 
      the highest risk for the development of the autoimmune skin disease psoriasis. 
      However, the diversity and mode of peptide presentation by the HLA-C*06:02 
      molecule remains unclear. Here, we describe the endogenous peptide repertoire of 
       approximately 3,000 sequences for HLA-C*06:02 that defines the peptide-binding motif for this 
      HLA allomorph. We found that HLA-C*06:02 predominantly presents nonamer peptides 
      with dominant arginine anchors at the P2 and P7 positions and a preference for 
      small hydrophobic residues at the C terminus (POmega). To determine the structural 
      basis of this selectivity, we determined crystal structures of HLA-C*06:02 in 
      complex with two self-peptides (ARTELYRSL and ARFNDLRFV) and an analogue of a 
      melanocyte autoantigen (ADAMTSL5, VRSRR-abu-LRL) implicated in psoriasis. These 
      structures revealed that HLA-C*06:02 possesses a deep peptide-binding groove 
      comprising two electronegative B- and E-pockets that coincide with the preference 
      for P2 and P7 arginine anchors. The ADAMTSL5 autoantigen possessed a P7-Leu 
      instead of the P7-Arg residue, but nevertheless was accommodated within the 
      HLA-C*06:02 antigen-binding cleft. Collectively, our results provide the 
      structural basis for understanding peptide repertoire selection in HLA-C*06:02.
CI  - (c) 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
FAU - Mobbs, Jesse I
AU  - Mobbs JI
AD  - From the Infection and Immunity Program and Department of Biochemistry and 
      Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton 
      3800, Victoria, Australia.
FAU - Illing, Patricia T
AU  - Illing PT
AD  - From the Infection and Immunity Program and Department of Biochemistry and 
      Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton 
      3800, Victoria, Australia.
FAU - Dudek, Nadine L
AU  - Dudek NL
AD  - From the Infection and Immunity Program and Department of Biochemistry and 
      Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton 
      3800, Victoria, Australia.
FAU - Brooks, Andrew G
AU  - Brooks AG
AD  - the Department of Microbiology and Immunology, University of Melbourne, Peter 
      Doherty Institute for Infection and Immunity, Melbourne 3000, Australia.
FAU - Baker, Daniel G
AU  - Baker DG
AD  - Janssen Research & Development, LLC, Horsham, Philadelphia, Pennsylvania 19044.
FAU - Purcell, Anthony W
AU  - Purcell AW
AD  - From the Infection and Immunity Program and Department of Biochemistry and 
      Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton 
      3800, Victoria, Australia, Anthony.purcell@monash.edu.
FAU - Rossjohn, Jamie
AU  - Rossjohn J
AD  - From the Infection and Immunity Program and Department of Biochemistry and 
      Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton 
      3800, Victoria, Australia, Jamie.rossjohn@monash.edu.
AD  - the Australian Research Council Centre of Excellence in Advanced Molecular 
      Imaging, Monash University, Clayton 3800, Victoria, Australia, and.
AD  - the Institute of Infection and Immunity, Cardiff University, School of Medicine, 
      Cardiff CF14 4XN, Wales, United Kingdom.
FAU - Vivian, Julian P
AU  - Vivian JP
AD  - From the Infection and Immunity Program and Department of Biochemistry and 
      Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton 
      3800, Victoria, Australia, Julian.vivian@monash.edu.
AD  - the Australian Research Council Centre of Excellence in Advanced Molecular 
      Imaging, Monash University, Clayton 3800, Victoria, Australia, and.
LA  - eng
SI  - PDB/5W6A
SI  - PDB/5W69
SI  - PDB/5W67
SI  - PDB/1EFX
SI  - PDB/1QQD
SI  - PDB/5VGD
SI  - PDB/5VGE
SI  - PDB/4NT6
SI  - PDB/3BP4
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170830
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (HLA-C Antigens)
RN  - 0 (HLA-C*06:02 antigen)
RN  - 0 (Peptides)
RN  - EC 3.4.24.- (ADAMTS Proteins)
RN  - EC 3.4.24.- (ADAMTSL5 protein, human)
SB  - IM
MH  - *ADAMTS Proteins/chemistry/genetics/immunology/metabolism
MH  - Amino Acid Motifs
MH  - *Antigen Presentation
MH  - Cell Line
MH  - *HLA-C Antigens/chemistry/genetics/immunology/metabolism
MH  - Humans
MH  - *Peptides/chemistry/genetics/immunology/metabolism
PMC - PMC5655500
OTO - NOTNLM
OT  - X-ray crystallography
OT  - autoimmunity
OT  - major histocompatibility complex (MHC)
OT  - mass spectrometry (MS)
OT  - psoriasis
COIS- This work was supported by Janssen Pty. Ltd D. G. B. is an employee of Janssen 
      Pty Ltd., which provided support for this work
EDAT- 2017/09/01 06:00
MHDA- 2017/10/27 06:00
PMCR- 2018/10/20
CRDT- 2017/09/01 06:00
PHST- 2017/07/14 00:00 [received]
PHST- 2017/08/18 00:00 [revised]
PHST- 2017/09/01 06:00 [pubmed]
PHST- 2017/10/27 06:00 [medline]
PHST- 2017/09/01 06:00 [entrez]
PHST- 2018/10/20 00:00 [pmc-release]
AID - S0021-9258(20)33881-3 [pii]
AID - M117.806976 [pii]
AID - 10.1074/jbc.M117.806976 [doi]
PST - ppublish
SO  - J Biol Chem. 2017 Oct 20;292(42):17203-17215. doi: 10.1074/jbc.M117.806976. Epub 
      2017 Aug 30.