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 ….