View
217
Download
2
Category
Tags:
Preview:
Citation preview
Animal derived allergenic molecules
Christiane Hilger
Laboratory of Immunogenetics and AllergologyCRP-Santé Luxembourg
http://www.meduniwien.ac.at/allergens/allfam/
Allergens are classified into families
Animal allergen families
Tropomyosins
Lipocalins
PR-1 proteins
Trypsin-like serine proteases
EF hand domains
Caseins
Serum albumins
Group 2 mite allergens
Globins
Lipases
Phospholipases A2
27
20
20
16
14
12
12
11
9
8
5
Allergen families: Tropomyosin
• Biochemical properties– Regulates muscle contraction, also present in non-muscle cells– Alpha-helical protein, MW 35-38 kDa– Identified as food allergens in crustaceans, molluscs and the fish
parasite Anisakis simplex– Identified as inhalant allergens in arthropods (mites,
cockroaches)– Highly conserved molecules, frequent cross-sensitisations– Vertebrate tropomyosins seem to be non-allergic
• Examples– Der p 10, Bla g 7
– Pen a 1 (shrimp), Hel as 1 (snail), Hom a 1 (lobster)
Rabbit tropomyosin dimer
• Biochemical properties– Transporters for small hydrophobic molecules, such as lipids,
steroids, odorants and pheromons– Low sequence identity between lipocalins – Eight-stranded anti-parallel -barrel– Constitute the vast majority of mammalian dander allergens
(inhalant allergen)– – lactoglobulins of ruminants (food allergen)
• Examples– – lactoglobulins: Bos d 5, – Mammalian dander : Can f 1, Can f 2, Fel d 4, Bos d 2, Equ c 1,
Mus m 1, Rat n 1– Group 13 mite allergens, cockroach Bla g 4– Pigeon tick major allergen Arg r 1
systemic allergen Equ c 1 dimer
Allergen families: Lipocalins
• Biochemical properties– Ca 2+ binding proteins that share a 12 aa conserved calcium-
binding loop, flanked by -helices on both sides
• Examples– Parvalbumins: major allergens of fish (Gad c 1, Sal s 1) and
amphibians (Ran e 1 , Ran e 2)– Troponin C : group 6 allergens in cockroaches (Bla g 6)– Cattle: Bos d 3 (inhalant allergen)
Allergen families: EF hand domain
Carp parvalbumin Cyp c 1 dimer
• Biochemical properties– Main plasma protein, MW 66 kDa– Binds water, cations, fatty acids, hormones, bilirubin, drugs– Regulates colloidal osmotic pressure of blood– Inhalant allergen of animal dander and saliva– Food allergen in meat, egg and milk
• Examples– Dander: Fel d 2 , Can f 3, Equ c 3, Bos d 6, Gal d 5– Food: Bos d 6, Gal d 5, PSA, SSA
Serum albumins are minor allergens, but they are reponsible for large interspecies cross-sensitisations
Allergen families: Serum albumins
Human serum albumin dimer
Mammalian allergens: Felis domesticus
• Fel d 1: Tetramer formed by 2 heterodimers consisting
each of chain 1 and 2; chains of 70 and 92 aa
MW = 38 kDa
glycosylated protein present in saliva
96% IgE positive (n=509), marker allergen
• Fel d 2: Serum albumin, 66 kDa
present in saliva, dander, urine
17-35% IgE positive
Cross-reactivities with Can f 3, Equ c 3, Sus sPSA, Bos d 6
• Fel d 3: Cystatin, cysteine protease inhibitor, 98 aa, 11 kDa
isolated from skin cDNA
10 % IgE positive
Mammalian allergens: Felis domesticus
• Fel d 4: Lipocalin, 171 aa , 19.7 kDaisolated from salivary gland63 % IgE positive, low IgE values
Homologies: Bos d 2, Can f 1, Equ c 1, Mus m1, Rat n 1
• Fel d 5: IgA, MW = 400 kDa present in serum38% IgE positive (n=81)
• Fel d 6: IgM, MW = 800 kDapresent in serum
• Fel d 7: IgG, MW = 150 kDapresent in serum
Mammalian allergens: Canis familiaris
• Can f 1: Lipocalin, MW = 23-25 kDa present in dander, saliva52-75 % IgE positive
• Can f 2: Lipocalin, MW = 19 kDapresent in dander, saliva20-32 % IgE positive
• Can f 3: Serum albumin, MW = 65 kDa present in dander, saliva, serum35-48 % IgE positiveCross-reactivities with Fel d 2, Equ c 3, Sus sPSA, Bos d 6 and other albumins
• Can f 4: N-terminal sequence known, 18 kDa60 % IgE positive
Can f 1 and 2 are available as recombinant molecules, but the combination of these 2 does not allow to diagnose all patients
Mammalian allergens: Bos domesticus
• Bos d 2: Lipocalin, MW = 20 kDa (former BDA 20)present in dander, inhalant allergen100 % IgE positive
• Bos d 3: S100 calcium binding protein A7, MW = 11 kDa, present in dander, inhalant allergen
• Bos d 4: Alpha-lactalbumin, MW = 14.2 kDapresent in milk, inhalant and food allergen70-90 % IgE positive (Europe)
• Bos d 5: Beta-lactoglobulin, MW = 18.3 kDa present in milk, inhalant and food allergen70-90 % IgE positive (Europe)
• Bos d 6: Serum albumin, MW = 67 kDa present in serum, milk, meat, dander, inhalant and food allergen48 % IgE positive Cross-reactivities with other albumins
Poultry allergens: Gallus domesticus
• Gal d 1: Ovomucoid, Trypsin inhibitor, MW = 28 kDa30-40 % IgE positive
• Gal d 2:Ovalbumin, MW = 44 kDa35 % IgE positive
• Gal d 3: Ovotransferrin, MW = 78 kDa53 % IgE positive
• Gal d 4:Lysozyme, MW = 14 kDa6 - 34 % IgE positive
• Gal d 5:serum albumin, MW = 69 kDa, formerly alpha-livetin present in serum, meat, dander and egg yolk
responsible for bird - egg syndrome• Gal d apovitellin: MW = 9 kDa
23 % IgE positive
Gal d 1 to Gal d 4 are food allergens of the egg white
Arthropod food and inhalant allergens: Crabs, Shrimps, Lobster
Cockroaches, Mites, Midges Tropomyosins are highly cross-reactive molecules found in different
arthropod and mollusc species:
Food allergensPen a 1: Penaeus aztecus, brown shrimpPan s 1: Panulirus stimpsoni, spiny lobsterCha f 1:Charybdis feriatus, crab
Inhalant allergensBla g 7: Blattella germanica, German cockroachDer p 10: Dermatophagoïdes pteronyssinus, Europ house dust miteChi k 10: Chironomus kiiensis, midge
.
.And many others ….
Recommended