Laboratory of Immunogenetics and Allergology
CRPSanté Luxembourg
Allergens are classified into families http://www.meduniwien.ac.at/allergens/allfam/
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
• 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 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
• 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
• 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
• 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
• 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
• 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
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• 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
• 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
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 ….