PMID- 37330172
OWN - NLM
STAT- MEDLINE
DCOM- 20230731
LR  - 20230731
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 299
IP  - 7
DP  - 2023 Jul
TI  - Complimentary electrostatics dominate T-cell receptor binding to a 
      psoriasis-associated peptide antigen presented by human leukocyte antigen 
      C *06:02.
PG  - 104930
LID - S0021-9258(23)01958-0 [pii]
LID - 10.1016/j.jbc.2023.104930 [doi]
LID - 104930
AB  - Psoriasis is a chronic skin disease characterized by hyperproliferative epidermal 
      lesions infiltrated by autoreactive T cells. Individuals expressing the human 
      leukocyte antigen (HLA) C *06:02 allele are at highest risk for developing 
      psoriasis. An autoreactive T cell clone (termed Valpha3S1/Vbeta13S1) isolated from 
      psoriatic plaques is selective for HLA-C *06:02, presenting a peptide derived from 
      the melanocyte-specific autoantigen ADAMTSL5 (VRSRRCLRL). Here we determine the 
      crystal structure of this psoriatic TCR-HLA-C *06:02 ADAMTSL5 complex with a 
      stabilized peptide. Docking of the TCR involves an extensive complementary charge 
      network formed between negatively charged TCR residues interleaving with exposed 
      arginine residues from the self-peptide and the HLA-C *06:02 alpha1 helix. We probed 
      these interactions through mutagenesis and activation assays. The charged 
      interface spans the polymorphic region of the C1/C2 HLA group. Notably the 
      peptide-binding groove of HLA-C *06:02 appears exquisitely suited for presenting 
      highly charged Arg-rich epitopes recognized by this acidic psoriatic TCR. 
      Overall, we provide a structural basis for understanding the engagement of 
      melanocyte antigen-presenting cells by a TCR implicated in psoriasis while 
      simultaneously expanding our knowledge of how TCRs engage HLA-C.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Anand, Sushma
AU  - Anand S
AD  - Infection and Immunity Program & Department of Biochemistry and Molecular 
      Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 
      Australia.
FAU - Littler, Dene R
AU  - Littler DR
AD  - Infection and Immunity Program & Department of Biochemistry and Molecular 
      Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 
      Australia.
FAU - Mobbs, Jesse I
AU  - Mobbs JI
AD  - Infection and Immunity Program & Department of Biochemistry and Molecular 
      Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 
      Australia.
FAU - Braun, Asolina
AU  - Braun A
AD  - Infection and Immunity Program & Department of Biochemistry and Molecular 
      Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 
      Australia.
FAU - Baker, Daniel G
AU  - Baker DG
AD  - Janssen Research & Development, LLC, Philadelphia, Pennsylvania, USA.
FAU - Tennant, Luke
AU  - Tennant L
AD  - Infection and Immunity Program & Department of Biochemistry and Molecular 
      Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 
      Australia.
FAU - Purcell, Anthony W
AU  - Purcell AW
AD  - Infection and Immunity Program & Department of Biochemistry and Molecular 
      Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 
      Australia.
FAU - Vivian, Julian P
AU  - Vivian JP
AD  - Infection and Immunity Program & Department of Biochemistry and Molecular 
      Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 
      Australia.
FAU - Rossjohn, Jamie
AU  - Rossjohn J
AD  - Infection and Immunity Program & Department of Biochemistry and Molecular 
      Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 
      Australia; Institute of Infection and Immunity, School of Medicine, Cardiff 
      University, Cardiff, UK. Electronic address: Jamie.rossjohn@monash.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230615
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (HLA-C Antigens)
RN  - 0 (Peptides)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - EC 3.4.24.- (ADAMTSL5 protein, human)
RN  - EC 3.4.24.- (ADAMTS Proteins)
SB  - IM
MH  - Humans
MH  - *HLA-C Antigens
MH  - Static Electricity
MH  - Peptides/chemistry
MH  - *Psoriasis/pathology
MH  - Receptors, Antigen, T-Cell/genetics
MH  - ADAMTS Proteins
PMC - PMC10371836
OTO - NOTNLM
OT  - HLA-C *06:02
OT  - T-cell receptor
OT  - antigen presentation
OT  - autoimmunity
OT  - major histocompatibility complex (MHC)
OT  - psoriasis
COIS- Conflict of interest D. G. B is an employee of Janssen Pty Ltd. All other authors 
      declare that they no conflicts of interest with the contents of this article.
EDAT- 2023/06/18 01:07
MHDA- 2023/07/31 06:43
PMCR- 2023/06/15
CRDT- 2023/06/17 19:17
PHST- 2023/04/20 00:00 [received]
PHST- 2023/06/05 00:00 [revised]
PHST- 2023/06/13 00:00 [accepted]
PHST- 2023/07/31 06:43 [medline]
PHST- 2023/06/18 01:07 [pubmed]
PHST- 2023/06/17 19:17 [entrez]
PHST- 2023/06/15 00:00 [pmc-release]
AID - S0021-9258(23)01958-0 [pii]
AID - 104930 [pii]
AID - 10.1016/j.jbc.2023.104930 [doi]
PST - ppublish
SO  - J Biol Chem. 2023 Jul;299(7):104930. doi: 10.1016/j.jbc.2023.104930. Epub 2023 
      Jun 15.