Proteases as Th2 adjuvants.
Several cysteine and serine protease allergens have been cloned from house dust mites, including Der p 1, Der p 3, Der p 6, and Der p 9. A significant body of evidence suggests that these allergens mimic helper T (Th) 2 cell adjuvants. Der p 1 cleaves CD23 from activated B cells and CD25 from T cells. Der p 1 proteolytically degrades tight junctions in lung epithelium and causes release of proinflammatory cytokines from bronchial epithelial cells, mast cells, and basophils. These synergistic effects of mite enzyme allergens may promote IgE synthesis and have direct inflammatory effects on lung epithelium, which could explain why mite allergens are associated with asthma. The crystal structures of the proenzyme and mature forms of Der p 1 have been determined, as have the structures of other indoor allergens that are not enzymes (eg, Der p 2, Fel d 1, and Bla g 2). Cockroach allergens are strongly associated with asthma in US inner cities, yet none of the cockroach allergens that have been cloned are proteolytic enzymes. Thus although mite proteases allergens may act as Th2 adjuvants, a paradoxical effect is that other allergens may elicit strong Th2 responses in the absence of enzyme activity.
Chapman
Martin D
MD
INDOOR Biotechnologies, Inc., 1216 Harris Street, Charlottesville, VA 22903, USA. mdc@inbio.com
Wünschmann
Sabina
S
Pomés
Anna
A
D000276:Adjuvants, Immunologic / Q000378:metabolism; D000485:Allergens / Q000276:immunology; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology*; D001249:Asthma / Q000276:immunology*; D003546:Cysteine Endopeptidases / Q000276:immunology*; D006801:Humans; D039981:Pyroglyphidae / Q000201:enzymology*; D012697:Serine Endopeptidases / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000485:Allergens; D039741:Antigens, Dermatophagoides; D012697:Serine Endopeptidases; D003546:Cysteine Endopeptidases
Eur J Immunol. 1996 Dec;26(12 ):2972-80
8977293
J Immunol. 2005 Sep 15;175(6):3835-45
16148130
Eur J Immunol. 1995 Nov;25(11):3191-4
7489763
J Immunol. 2006 Aug 1;177(3):1609-17
16849469
Int Arch Allergy Immunol. 2003 Jan;130(1):12-6
12576730
Biochem Biophys Res Commun. 2005 Mar 25;328(4):944-52
15707969
Protein Expr Purif. 2000 Dec;20(3):462-71
11087686
Clin Exp Allergy. 2001 Feb;31(2):279-94
11251630
N Engl J Med. 2003 Oct 9;349(15):1414-22
14534334
J Allergy Clin Immunol. 2005 Jul;116(1):140-5
15990787
J Clin Invest. 1999 Jul;104(1):123-33
10393706
N Engl J Med. 2004 Sep 9;351(11):1068-80
15356304
J Exp Med. 1998 Jan 19;187(2):271-5
9432986
J Exp Med. 1995 Nov 1;182(5):1537-44
7595223
J Exp Med. 1999 Dec 20;190(12):1897-902
10601364
J Immunol. 2001 Jul 15;167(2):1014-21
11441110
Immunol Today. 1998 Jul;19(7):313-6
9666604
Clin Exp Allergy. 2003 Feb;33(2):163-5
12580906
J Mol Biol. 2005 Apr 29;348(2):433-44
15811379
J Allergy Clin Immunol. 1996 Oct;98(4):739-47
8876548
J Biol Chem. 2003 Sep 26;278(39):37730-5
12851385
J Biol Chem. 2004 Jul 2;279(27):28475-82
15111623
Clin Exp Allergy. 2001 Oct;31(10):1594-8
11678860
J Allergy Clin Immunol. 1998 Jul;102(1):75-85
9679850
J Allergy Clin Immunol. 2007 Feb;119(2):414-20
17166572
FEBS Lett. 1995 Dec 11;377(1):62-6
8543021
Am J Respir Crit Care Med. 2002 Feb 1;165(3):391-7
11818327
J Allergy Clin Immunol. 2005 Mar;115(3):555-63
15753904
Annu Rev Entomol. 2007;52:439-63
17163801
J Allergy Clin Immunol. 2006 Mar;117(3):571-6
16522455
J Allergy Clin Immunol. 2005 Apr;115(4):803-9
15806002
Clin Exp Allergy. 1996 Oct;26(10):1150-4
8911700
J Allergy Clin Immunol. 2005 Mar;115(3):478-85
15753892
Insect Mol Biol. 2005 Jan;14 (1):45-53
15663774
J Exp Med. 1988 Jan 1;167(1):175-82
3335830
J Allergy Clin Immunol. 2000 Sep;106(3):409-18
10984358
J Immunol. 2002 Oct 15;169(8):4572-8
12370395
Eur J Biochem. 2002 Jan;269(2):671-9
11856327
J Immunol. 1998 Oct 1;161(7):3645-51
9759888
Clin Exp Allergy. 1997 Jan;27(1):10-21
9117873