Animal derived allergenic molecules

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Animal derived allergenic molecules

Christiane Hilger

Laboratory of Immunogenetics and Allergology

CRPSanté Luxembourg

Allergens are classified into families http://www.meduniwien.ac.at/allergens/allfam/

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 5

9

8

16

14

12

12

11

20

20

27

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

Allergen families: Lipocalins

• Biochemical properties

– Transporters for small hydrophobic molecules, such as lipids, steroids, odorants and pheromons

– Low sequence identity between lipocalins

– Eight-stranded anti-parallel b

-barrel

– Constitute the vast majority of mammalian dander allergens

( inhalant allergen )

– b – lactoglobulins of ruminants ( food allergen )

• Examples

– b – 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: EF hand domain

• Biochemical properties

– Ca 2+ binding proteins that share a 12 aa conserved calciumbinding loop, flanked by a

-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)

Carp parvalbumin Cyp c 1 dimer

Allergen families: Serum albumins

• 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

Human serum albumin dimer

Mammalian allergens: Felis domesticus

• Fel d 1:

• Fel d 2:

• Fel d 3:

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

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

Cystatin, cysteine protease inhibitor, 98 aa, 11 kDa isolated from skin cDNA

10 % IgE positive

Mammalian allergens: Felis domesticus

• Fel d 4:

• Fel d 5:

• Fel d 6:

• Fel d 7:

Lipocalin , 171 aa , 19.7 kDa isolated from salivary gland

63 % IgE positive, low IgE values

Homologies: Bos d 2, Can f 1, Equ c 1, Mus m1, Rat n 1

IgA, MW = 400 kDa present in serum

38% IgE positive (n=81)

IgM, MW = 800 kDa present in serum

IgG, MW = 150 kDa present in serum

Mammalian allergens: Canis familiaris

• Can f 1: Lipocalin , MW = 23-25 kDa present in dander, saliva

52-75 % IgE positive

• Can f 2: Lipocalin , MW = 19 kDa present in dander, saliva

20-32 % IgE positive

• Can f 3: Serum albumin, MW = 65 kDa present in dander, saliva, serum

35-48 % IgE positive

Cross-reactivities with Fel d 2, Equ c 3, Sus sPSA, Bos d 6 and other albumins

• Can f 4: N-terminal sequence known, 18 kDa

60 % 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:

Bos d 3:

Bos d 4:

Bos d 5:

Bos d 6:

Lipocalin , MW = 20 kDa (former BDA 20) present in dander, inhalant allergen

100 % IgE positive

S100 calcium binding protein A7, MW = 11 kDa, present in dander, inhalant allergen

Alpha-lactalbumin, MW = 14.2 kDa present in milk, inhalant and food allergen

70-90 % IgE positive (Europe)

Beta-lactoglobulin , MW = 18.3 kDa present in milk, inhalant and food allergen

70-90 % IgE positive (Europe)

Serum albumin, MW = 67 kDa present in serum, milk, meat, dander, inhalant and food allergen

48 % IgE positive

Cross-reactivities with other albumins

Poultry allergens: Gallus domesticus

• Gal d 1: Ovomucoid, Trypsin inhibitor, MW = 28 kDa

30-40 % IgE positive

• Gal d 2: Ovalbumin, MW = 44 kDa

35 % IgE positive

• Gal d 3: Ovotransferrin, MW = 78 kDa

53 % IgE positive

• Gal d 4: Lysozyme, MW = 14 kDa

6 - 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 allergens

Pen a 1: Penaeus aztecus , brown shrimp

Pan s 1:

Cha f 1:

Panulirus stimpsoni

Charybdis feriatus

, spiny lobster

, crab

Inhalant allergens

Bla g 7: Blattella germanica , German cockroach

Der p 10: Dermatophagoïdes pteronyssinus, Europ house dust mite

Chi k 10: Chironomus kiiensis , midge

.

.

And many others ….

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