PMID- 26621454
OWN - NLM
STAT- MEDLINE
DCOM- 20160523
LR  - 20181113
IS  - 1540-9538 (Electronic)
IS  - 0022-1007 (Print)
IS  - 0022-1007 (Linking)
VI  - 212
IP  - 13
DP  - 2015 Dec 14
TI  - Melanocyte antigen triggers autoimmunity in human psoriasis.
PG  - 2203-12
LID - 10.1084/jem.20151093 [doi]
AB  - Psoriasis vulgaris is a common T cell-mediated inflammatory skin disease with a 
      suspected autoimmune pathogenesis. The human leukocyte antigen (HLA) class I 
      allele, HLA-C*06:02, is the main psoriasis risk gene. Epidermal CD8(+) T cells 
      are essential for psoriasis development. Functional implications of HLA-C*06:02 
      and mechanisms of lesional T cell activation in psoriasis, however, remained 
      elusive. Here we identify melanocytes as skin-specific target cells of an 
      HLA-C*06:02-restricted psoriatic T cell response. We found that a Valpha3S1/Vbeta13S1 T 
      cell receptor (TCR), which we had reconstituted from an epidermal CD8(+) T cell 
      clone of an HLA-C*06:02-positive psoriasis patient specifically recognizes 
      HLA-C*06:02-positive melanocytes. Through peptide library screening, we 
      identified ADAMTS-like protein 5 (ADAMTSL5) as an HLA-C*06:02-presented 
      melanocytic autoantigen of the Valpha3S1/Vbeta13S1 TCR. Consistent with the 
      Valpha3S1/Vbeta13S1-TCR reactivity, we observed numerous CD8(+) T cells in psoriasis 
      lesions attacking melanocytes, the only epidermal cells expressing ADAMTSL5. 
      Furthermore, ADAMTSL5 stimulation induced the psoriasis signature cytokine, 
      IL-17A, in CD8(+) T cells from psoriasis patients only, supporting a role as 
      psoriatic autoantigen. This unbiased analysis of a TCR obtained directly from 
      tissue-infiltrating CD8(+) T cells reveals that in psoriasis HLA-C*06:02 directs 
      an autoimmune response against melanocytes through autoantigen presentation. We 
      propose that HLA-C*06:02 may predispose to psoriasis via this newly identified 
      autoimmune pathway.
CI  - (c) 2015 Arakawa et al.
FAU - Arakawa, Akiko
AU  - Arakawa A
AD  - Department of Dermatology, Ludwig-Maximilian-University, D-80337 Munich, Germany.
FAU - Siewert, Katherina
AU  - Siewert K
AD  - Institute of Clinical Neuroimmunology, Ludwig-Maximilian-University, D-82152 
      Planegg-Martinsried, Germany.
FAU - Stohr, Julia
AU  - Stohr J
AD  - Department of Dermatology, Ludwig-Maximilian-University, D-80337 Munich, Germany.
FAU - Besgen, Petra
AU  - Besgen P
AD  - Department of Dermatology, Ludwig-Maximilian-University, D-80337 Munich, Germany.
FAU - Kim, Song-Min
AU  - Kim SM
AD  - Department of Dermatology, Ludwig-Maximilian-University, D-80337 Munich, Germany.
FAU - Ruhl, Geraldine
AU  - Ruhl G
AD  - Institute of Clinical Neuroimmunology, Ludwig-Maximilian-University, D-82152 
      Planegg-Martinsried, Germany.
FAU - Nickel, Jens
AU  - Nickel J
AD  - Department of Dermatology, Ludwig-Maximilian-University, D-80337 Munich, Germany.
FAU - Vollmer, Sigrid
AU  - Vollmer S
AD  - Department of Dermatology, Ludwig-Maximilian-University, D-80337 Munich, Germany.
FAU - Thomas, Peter
AU  - Thomas P
AD  - Department of Dermatology, Ludwig-Maximilian-University, D-80337 Munich, Germany.
FAU - Krebs, Stefan
AU  - Krebs S
AD  - Gene Center Munich, Ludwig-Maximilian-University, D-81377 Munich, Germany.
FAU - Pinkert, Stefan
AU  - Pinkert S
AD  - German Cancer Research Center, D-69120 Heidelberg, Germany.
FAU - Spannagl, Michael
AU  - Spannagl M
AD  - Laboratory of Immunogenetics and Molecular Diagnostics, 
      Ludwig-Maximilian-University, D-81377 Munich, Germany.
FAU - Held, Kathrin
AU  - Held K
AD  - Institute of Clinical Neuroimmunology, Ludwig-Maximilian-University, D-82152 
      Planegg-Martinsried, Germany.
FAU - Kammerbauer, Claudia
AU  - Kammerbauer C
AD  - Department of Dermatology, Ludwig-Maximilian-University, D-80337 Munich, Germany.
FAU - Besch, Robert
AU  - Besch R
AD  - Department of Dermatology, Ludwig-Maximilian-University, D-80337 Munich, Germany.
FAU - Dornmair, Klaus
AU  - Dornmair K
AD  - Institute of Clinical Neuroimmunology, Ludwig-Maximilian-University, D-82152 
      Planegg-Martinsried, Germany.
FAU - Prinz, Jorg C
AU  - Prinz JC
AD  - Department of Dermatology, Ludwig-Maximilian-University, D-80337 Munich, Germany 
      joerg.prinz@med.uni-muenchen.de.
LA  - eng
SI  - PIR/MIM177900
SI  - RefSeq/NP_998769
SI  - SWISSPROT/A6NK89
SI  - SWISSPROT/A6NLJ0
SI  - SWISSPROT/Q14CZ8
SI  - SWISSPROT/Q8WUY1
SI  - SWISSPROT/Q9NR48
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151130
PL  - United States
TA  - J Exp Med
JT  - The Journal of experimental medicine
JID - 2985109R
RN  - 0 (Autoantigens)
RN  - 0 (Epitopes)
RN  - 0 (HLA-C Antigens)
RN  - 0 (Peptides)
RN  - 0 (Receptors, Antigen, T-Cell, alpha-beta)
RN  - EC 3.4.24.- (ADAM Proteins)
RN  - EC 3.4.24.- (ADAMTS Proteins)
RN  - EC 3.4.24.- (ADAMTSL5 protein, human)
SB  - IM
CIN - J Exp Med. 2015 Dec 14;212(13):2186. PMID: 26666753
CIN - Pigment Cell Melanoma Res. 2016 May;29(3):261-3. PMID: 26929278
MH  - ADAM Proteins/metabolism
MH  - ADAMTS Proteins
MH  - Adult
MH  - Amino Acid Sequence
MH  - Autoantigens/*immunology
MH  - Autoimmunity/*immunology
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Cell Line
MH  - Epidermis/metabolism/pathology
MH  - Epitopes/chemistry/immunology
MH  - Female
MH  - HLA-C Antigens/immunology
MH  - Humans
MH  - Male
MH  - Melanocytes/*metabolism
MH  - Molecular Sequence Data
MH  - Peptides/chemistry
MH  - Psoriasis/*immunology
MH  - Receptors, Antigen, T-Cell, alpha-beta/metabolism
PMC - PMC4689169
EDAT- 2015/12/02 06:00
MHDA- 2016/05/24 06:00
PMCR- 2016/06/14
CRDT- 2015/12/02 06:00
PHST- 2015/07/02 00:00 [received]
PHST- 2015/11/04 00:00 [accepted]
PHST- 2015/12/02 06:00 [entrez]
PHST- 2015/12/02 06:00 [pubmed]
PHST- 2016/05/24 06:00 [medline]
PHST- 2016/06/14 00:00 [pmc-release]
AID - jem.20151093 [pii]
AID - 20151093 [pii]
AID - 10.1084/jem.20151093 [doi]
PST - ppublish
SO  - J Exp Med. 2015 Dec 14;212(13):2203-12. doi: 10.1084/jem.20151093. Epub 2015 Nov 
      30.