PMID- 17250696
OWN - NLM
STAT- MEDLINE
DCOM- 20070813
LR  - 20111117
IS  - 0954-7894 (Print)
IS  - 0954-7894 (Linking)
VI  - 37
IP  - 2
DP  - 2007 Feb
TI  - The protease allergen Der p 1 cleaves cell surface DC-SIGN and DC-SIGNR: 
      experimental analysis of in silico substrate identification and implications in 
      allergic responses.
PG  - 231-42
AB  - BACKGROUND: The cysteine protease Der p 1 from the house dust mite 
      Dermatophagoides pteronyssinus is one of the most potent allergens known. An 
      attractive mechanism for a component of Der p 1 allergenicity lies in its ability 
      to cleave key regulatory molecules from leucocyte surfaces, subverting cellular 
      function and driving abnormal immunoglobulin E (IgE) responses. OBJECTIVE: 
      Although CD23, CD25 and CD40 have already been identified as major Der p 1 
      targets, other significant substrates may also exist. METHODS: To investigate 
      this, knowledge of the proteolytic properties of Der p 1 was used to perform in 
      silico digestion of human dendritic cell surface proteins, using the prediction 
      of protease specificity (PoPS) bioinformatics tool, in conjunction with cellular 
      in vitro analysis and cleavage site determination. RESULTS: Targets identified 
      included DC-SIGN and DC-SIGNR, two C-type lectins implicated mostly in pathogen 
      trafficking. Treatment of positively expressing cells with Der p 1 led to loss of 
      detectable surface DC-SIGN and DC-SIGNR. Digestion of purified soluble 
      recombinant DC-SIGN and DC-SIGNR, followed by N-terminal sequencing and MALDI 
      mass spectrometry, indicated in each case one major cleavage site and several 
      minor sites, the former correlating well with Der p 1 enzymology and the folded 
      state of the substrate proteins. Loss of DC-SIGN from the cell surface led to 
      reduced binding of intracellular adhesion molecule-3, an endogenous DC-SIGN 
      ligand expressed on naive T cells which is thought to be involved in T-helper 
      type 1 cytokine signalling. CONCLUSION: These data provide evidence of lectin 
      involvement in the initiation of the allergic response and the value of using 
      genome-wide in silico digestion tools.
FAU - Furmonaviciene, R
AU  - Furmonaviciene R
AD  - Institute of Infection, Immunity and Inflammation, School of Molecular Medical 
      Sciences, University of Nottingham, Nottingham, UK.
FAU - Ghaemmaghami, A M
AU  - Ghaemmaghami AM
FAU - Boyd, S E
AU  - Boyd SE
FAU - Jones, N S
AU  - Jones NS
FAU - Bailey, K
AU  - Bailey K
FAU - Willis, A C
AU  - Willis AC
FAU - Sewell, H F
AU  - Sewell HF
FAU - Mitchell, D A
AU  - Mitchell DA
FAU - Shakib, F
AU  - Shakib F
LA  - eng
GR  - U54RR020843/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Clin Exp Allergy
JT  - Clinical and experimental allergy : journal of the British Society for Allergy 
      and Clinical Immunology
JID - 8906443
RN  - 0 (Allergens)
RN  - 0 (Antigens, Dermatophagoides)
RN  - 0 (Arthropod Proteins)
RN  - 0 (CLEC4M protein, human)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (DC-specific ICAM-3 grabbing nonintegrin)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Receptors, Cell Surface)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
RN  - EC 3.4.22.- (Dermatophagoides pteronyssinus antigen p 1)
SB  - IM
MH  - Allergens/immunology
MH  - Animals
MH  - Antigens, Dermatophagoides/*immunology
MH  - Arthropod Proteins
MH  - Cell Adhesion Molecules/*immunology
MH  - Cysteine Endopeptidases
MH  - Dendritic Cells/*immunology
MH  - Humans
MH  - Lectins, C-Type/*immunology
MH  - Mice
MH  - Mites/*immunology
MH  - Receptors, Cell Surface/*immunology
EDAT- 2007/01/26 09:00
MHDA- 2007/08/19 09:00
CRDT- 2007/01/26 09:00
PHST- 2007/01/26 09:00 [pubmed]
PHST- 2007/08/19 09:00 [medline]
PHST- 2007/01/26 09:00 [entrez]
AID - CEA2651 [pii]
AID - 10.1111/j.1365-2222.2007.02651.x [doi]
PST - ppublish
SO  - Clin Exp Allergy. 2007 Feb;37(2):231-42. doi: 10.1111/j.1365-2222.2007.02651.x.