Mammalian lipocalin allergens - insights into their enigmatic allergenicity

Clinical and Experimental Allergy

Volumn 42, Issue 4, 2012, Pages 494-504

  Virtanen, T ^a   Kinnunen, T ^a   Rytkonen Nissinen M ^a  

^a UNIVERSITY OF EASTERN FINLAND   (Finland)

Author keywords

Allergen; Allergenicity; Animal allergen; Lipocalins; Mammal

Indexed keywords

ALLERGEN; BETA LACTOGLOBULIN; EPITOPE; GAMMA INTERFERON; IMMUNOGLOBULIN E; INTERLEUKIN 13; INTERLEUKIN 4; LIPOCALIN; LIPOPOLYSACCHARIDE; PLACENTA PROTEIN 14; T LYMPHOCYTE RECEPTOR;

ALLERGENICITY; AMINO ACID SEQUENCE; CELLULAR IMMUNITY; CROSS REACTION; CYTOKINE RELEASE; ENVIRONMENTAL EXPOSURE; ENZYME ACTIVITY; FOOD ALLERGY; HUMAN; IMMUNOBLOTTING; IMMUNOGLOBULIN PRODUCTION; LIGAND BINDING; MAJOR HISTOCOMPATIBILITY COMPLEX; MEMORY T LYMPHOCYTE; NONHUMAN; OCCUPATIONAL HAZARD; OLIGOMERIZATION; PRIORITY JOURNAL; PROTEIN ANALYSIS; RECEPTOR BINDING; REVIEW; TH2 CELL;

ALLERGENS; ANIMALS; HUMANS; HYPERSENSITIVITY, IMMEDIATE; LIPOCALINS;

EID: 84858339838     PISSN: 09547894     EISSN: 13652222     Source Type: Journal    
DOI: 10.1111/j.1365-2222.2011.03903.x     Document Type: Review

References (111)

1. Holt PG, Thomas WR. Sensitization to airborne environmental allergens: unresolved issues. Nat Immunol 2005; 6:957-60.
2. Akdis CA. Allergy and hypersensitivity: mechanisms of allergic disease. Curr Opin Immunol 2006; 18:718-26.
3. Platts-Mills TA. The role of indoor allergens in chronic allergic disease. J Allergy Clin Immunol 2007; 119:297-302.
4. Paul WE, Zhu J. How are T(H)2-type immune responses initiated and amplified? Nat Rev Immunol 2010; 10:225-35.
5. Mäntyjärvi R, Parkkinen S, Rytkönen M et al. Complementary DNA cloning of the predominant allergen of bovine dander: a new member in the lipocalin family. J Allergy Clin Immunol 1996; 97:1297-303.
6. Konieczny A, Morgenstern JP, Bizinkauskas CB et al. The major dog allergens, Can f 1 and Can f 2, are salivary lipocalin proteins: cloning and immunological characterization of the recombinant forms. Immunology 1997; 92:577-86.
7. Mattsson L, Lundgren T, Olsson P, Sundberg M, Lidholm J. Molecular and immunological characterization of Can f 4: a dog dander allergen cross-reactive with a 23 kDa odorant-binding protein in cow dander. Clin Exp Allergy 2010; 40:1276-87.
8. Fahlbusch B, Rudeschko O, Szilagyi U et al. Purification and partial characterization of the major allergen, Cav p 1, from guinea pig Cavia porcellus. Allergy 2002; 57:417-22.
9. Hilger C, Swiontek K, Kler S et al. Evaluation of two new recombinant guinea-pig lipocalins, Cav p 2 and Cav p 3, in the diagnosis of guinea-pig allergy. Clin Exp Allergy 2011; 41:899-908.
10. Gregoire C, Rosinski-Chupin I, Rabillon J, Alzari PM, David B, Dandeu JP. cDNA cloning and sequencing reveal the major horse allergen Equ c 1 to be a glycoprotein member of the lipocalin superfamily. J Biol Chem 1996; 271:32951-9.
11. Bulone V, Krogstad-Johnsen T, Smestad-Paulsen B. Separation of horse dander allergen proteins by two-dimensional electrophoresis - molecular characterisation and identification of Equ c 2.0101 and Equ c 2.0102 as lipocalin proteins. Eur J Biochem 1998; 253:202-11.
12. Smith W, Butler AJ, Hazell LA et al. Fel d 4, a cat lipocalin allergen. Clin Exp Allergy 2004; 34:1732-8.
13. Smith W, O'Neil SE, Hales BJ et al. Two newly identified cat allergens: the von Ebner gland protein Fel d 7 and the latherin-like protein Fel d 8. Int Arch Allergy Immunol 2011; 156:159-70.
14. 2U-globulins and aphrodisin. Biochim Biophys Acta 2000; 1482:218-28.
15. Baker J, Berry A, Boscato LM, Gordon S, Walsh BJ, Stuart MC. Identification of some rabbit allergens as lipocalins. Clin Exp Allergy 2001; 31:303-12.
16. Helm RM, Burks AW. Food allergens. In: Lockey RF, Ledford DK, eds. Allergens and allergen immunotherapy. New York: Informa Healthcare USA, Inc., 2008:219-35.
17. Arruda LK, Vailes LD, Hayden ML, Benjamin DC, Chapman MD. Cloning of cockroach allergen, Bla g 4, identifies ligand binding proteins (or calycins) as a cause of IgE antibody responses. J Biol Chem 1995; 270:31196-201.
18. Paddock CD, McKerrow JH, Hansell E, Foreman KW, Hsieh I, Marshall N. Identification, cloning, and recombinant expression of procalin, a major triatomine allergen. J Immunol 2001; 167:2694-9.
19. Hilger C, Bessot JC, Hutt N et al. IgE-mediated anaphylaxis caused by bites of the pigeon tick Argas reflexus: cloning and expression of the major allergen Arg r 1. J Allergy Clin Immunol 2005; 115:617-22.
20. Saarelainen S, Rytkönen-Nissinen M, Rouvinen J et al. Animal-derived lipocalin allergens exhibit immunoglobulin E cross-reactivity. Clin Exp Allergy 2008; 38:374-81.
21. Madhurantakam C, Nilsson OB, Uchtenhagen H et al. Crystal structure of the dog lipocalin allergen Can f 2: implications for cross-reactivity to the cat allergen Fel d 4. J Mol Biol 2010; 401:68-83.
22. Rouvinen J, Jänis J, Laukkanen ML et al. Transient dimers of allergens. PLoS ONE 2010; 5:e9037.
23. Ganfornina MD, Sanchez D, Greene LH, Flower DR. The lipocalin protein family: protein sequence, structure and relationship to the calycin superfamily. In: Åkerstrom B, Borregaard N, Flower D, Salier JP, eds. Lipocalins. Georgetown: Landes Bioscience, 2006:17-27.
24. Rachmilewitz J, Riely GJ, Huang JH, Chen A, Tykocinski ML. A rheostatic mechanism for T-cell inhibition based on elevation of activation thresholds. Blood 2001; 98:3727-32.
25. Åkerstrom B, Borregaard N, Flower D, Salier JP. Lipocalins: an introduction. In: Åkerstrom B, Borregaard N, Flower D, Salier JP, eds. Lipocalins. Georgetown: Landes Bioscience, 2006:1-4.
26. Flower DR, Skerra A. The lipocalin protein family: perspectives for future research. In: Åkerstrom B, Borregaard N, Flower D, Salier JP, eds. Lipocalins. Georgetown: Landes Bioscience, 2006:193-8.
27. Altschul SF, Madden TL, Schaffer AA et al. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 1997; 25:3389-402.
28. Rouvinen J, Rautiainen J, Virtanen T et al. Probing the molecular basis of allergy - three-dimensional structure of the bovine lipocalin allergen Bos d 2. J Biol Chem 1999; 274:2337-43.
29. Åkerstrom B, Flower DR, Salier JP. Lipocalins: unity in diversity. Biochim Biophys Acta 2000; 1482:1-8.
30. Virtanen T, Kinnunen T. Mammalian allergens. In: Lockey RF, Ledford DK, eds. Allergens and allergen immunotherapy. 4th Edn. New York: Informa Healthcare USA, Inc., 2008:201-18.
31. Ohtani T, Nakagawa S, Kurosawa M, Mizuashi M, Ozawa M, Aiba S. Cellular basis of the role of diesel exhaust particles in inducing Th2-dominant response. J Immunol 2005; 174:2412-9.
32. Boldogh I, Bacsi A, Choudhury BK et al. ROS generated by pollen NADPH oxidase provide a signal that augments antigen-induced allergic airway inflammation. J Clin Invest 2005; 115:2169-79.
33. Gilles S, Fekete A, Zhang X et al. Pollen metabolome analysis reveals adenosine as a major regulator of dendritic cell-primed T(H) cell responses. J Allergy Clin Immunol 2011; 127:454-61.
34. Traidl-Hoffmann C, Mariani V, Hochrein H et al. Pollen-associated phytoprostanes inhibit dendritic cell interleukin-12 production and augment T helper type 2 cell polarization. J Exp Med 2005; 201:627-36.
35. Gilles S, Mariani V, Bryce M et al. Pollen-derived E1-phytoprostanes signal via PPAR-gamma and NF-kappaB-dependent mechanisms. J Immunol 2009; 182:6653-8.
36. Thomas WR, Hales BJ, Smith WA. Structural biology of allergens. Curr Allergy Asthma Rep 2005; 5:388-93.
37. Heinrich J, Gehring U, Douwes J et al. Pets and vermin are associated with high endotoxin levels in house dust. Clin Exp Allergy 2001; 31:1839-45.
38. Waser M, Schierl R, von Mutius E et al. Determinants of endotoxin levels in living environments of farmers' children and their peers from rural areas. Clin Exp Allergy 2004; 34:389-97.
39. Ege MJ, Frei R, Bieli C et al. The Parsifal Study Team. Not all farming environments protect against the development of asthma and wheeze in children. J Allergy Clin Immunol 2007; 119:1140-7.
40. Dabbagh K, Dahl ME, Stepick-Biek P, Lewis DB. Toll-like receptor 4 is required for optimal development of Th2 immune responses: role of dendritic cells. J Immunol 2002; 168:4524-30.
41. Eisenbarth SC, Piggott DA, Huleatt JW, Visintin I, Herrick CA, Bottomly K. Lipopolysaccharide-enhanced, toll-like receptor 4-dependent T helper cell type 2 responses to inhaled antigen. J Exp Med 2002; 196:1645-51.
42. Ebeling C, Lam T, Gordon JR, Hollenberg MD, Vliagoftis H. Proteinase-activated receptor-2 promotes allergic sensitization to an inhaled antigen through a TNF-mediated pathway. J Immunol 2007; 179:2910-7.
43. Lamhamedi-Cherradi SE, Martin RE, Ito T et al. Fungal proteases induce Th2 polarization through limited dendritic cell maturation and reduced production of IL-12. J Immunol 2008; 180:6000-9.
44. Kouzaki H, O'Grady SM, Lawrence CB, Kita H. Proteases induce production of thymic stromal lymphopoietin by airway epithelial cells through protease-activated receptor-2. J Immunol 2009; 183:1427-34.
45. Maneechotesuwan K, Wamanuttajinda V, Kasetsinsombat K et al. Der p 1 suppresses indoleamine 2, 3-dioxygenase in dendritic cells from house dust mite-sensitive patients with asthma. J Allergy Clin Immunol 2009; 123:239-48.
46. Yusifov TN, Abduragimov AR, Gasymov OK, Glasgow BJ. Endonuclease activity in lipocalins. Biochem J 2000; 347:815-9.
47. Zeiler T, Mäntyjärvi R, Rautiainen J et al. T cell epitopes of a lipocalin allergen colocalize with the conserved regions of the molecule. J Immunol 1999; 162:1415-22.
48. Immonen A, Farci S, Taivainen A et al. T cell epitope-containing peptides of the major dog allergen Can f 1 as candidates for allergen immunotherapy. J Immunol 2005; 105:3614-20.
49. Yusifov TN, Abduragimov AR, Narsinh K, Gasymov OK, Glasgow BJ. Tear lipocalin is the major endonuclease in tears. Mol Vis 2008; 14:180-8.
50. Ichikawa K, Vailes LD, Pomes A, Chapman MD. Molecular cloning, expression and modelling of cat allergen, cystatin (Fel d 3), a cysteine protease inhibitor. Clin Exp Allergy 2001; 31:1279-86.
51. van't Hof W, Blankenvoorde MF, Veerman EC, Amerongen AV. The salivary lipocalin von Ebner's gland protein is a cysteine proteinase inhibitor. J Biol Chem 1997; 272:1837-41.
52. Shreffler WG, Castro RR, Kucuk ZY et al. The major glycoprotein allergen from Arachis hypogaea, Ara h 1, is a ligand of dendritic cell-specific ICAM-grabbing nonintegrin and acts as a Th2 adjuvant in vitro. J Immunol 2006; 177:3677-85.
53. Royer PJ, Emara M, Yang C et al. The mannose receptor mediates the uptake of diverse native allergens by dendritic cells and determines allergen-induced T cell polarization through modulation of IDO activity. J Immunol 2010; 185:1522-31.
54. Rachmilewitz J, Borovsky Z, Riely GJ, Miller R, Tykocinski ML. Negative regulation of T cell activation by placental protein 14 is mediated by the tyrosine phosphatase receptor CD45. J Biol Chem 2003; 278:14059-65.
55. Ish-Shalom E, Gargir A, Andre S et al. Alpha 2, 6-Sialylation promotes binding of placental protein 14 via its Ca2+-dependent lectin activity: insights into differential effects on CD45RO and CD45RA T cells. Glycobiology 2006; 16:173-83.
56. Mishan-Eisenberg G, Borovsky Z, Weber MC, Gazit R, Tykocinski ML, Rachmilewitz J. Differential regulation of TH1/TH2 cytokine responses by placental protein 14. J Immunol 2004; 173:5524-30.
57. Ochanuna Z, Geiger-Maor A, Dembinsky-Vaknin A, Karussis D, Tykocinski ML, Rachmilewitz J. Inhibition of effector function but not T cell activation and increase in FoxP3 expression in T cells differentiated in the presence of PP14. PLoS ONE 2010; 5:e12868.
58. Burke BJ, Redondo C, Redl B, Findlay JBC. Lipocalin receptors: into the spotlight. In: Åkerstrom B, Borregaard N, Flower D, Salier JP, eds. Lipocalins. Georgetown: Landes Bioscience, 2006:167-76.
59. Devireddy LR, Gazin C, Zhu X, Green MR. A cell-surface receptor for lipocalin 24p3 selectively mediates apoptosis and iron uptake. Cell 2005; 123:1293-305.
60. Kawaguchi R, Yu J, Honda J et al. A membrane receptor for retinol binding protein mediates cellular uptake of vitamin A. Science 2007; 315:820-5.
61. Fluckinger M, Merschak P, Hermann M, Haertle T, Redl B. Lipocalin-interacting-membrane-receptor (LIMR) mediates cellular internalization of beta-lactoglobulin. Biochim Biophys Acta 2008; 1778:342-7.
62. Kinnunen T, Taivainen A, Partanen J et al. The DR4-DQ8 haplotype and a specific TCR Vbeta T-cell subset are associated with absence of allergy to Can f 1. Clin Exp Allergy 2005; 35:797-803.
63. Immonen A, Kinnunen T, Sirven P et al. The horse major allergen Equ c 1 contains one immunodominant region of T cell epitopes. Clin Exp Allergy 2007; 37:939-47.
64. Jeal H, Draper A, Harris J, Taylor AN, Cullinan P, Jones M. Determination of the T cell epitopes of the lipocalin allergen, Rat n 1. Clin Exp Allergy 2004; 34:1919-25.
65. Saarelainen S, Zeiler T, Rautiainen J et al. Lipocalin allergen Bos d 2 is a weak immunogen. Int Immunol 2002; 14:401-9.
66. Immonen A, Saarelainen S, Rautiainen J et al. Probing the mechanisms of low immunogenicity of a lipocalin allergen, Bos d 2, in a mouse model. Clin Exp Allergy 2003; 33:834-41.
67. Parviainen S, Taivainen A, Liukko A et al. Comparison of the allergic and nonallergic CD4(+) T-cell responses to the major dog allergen Can f 1. J Allergy Clin Immunol 2010; 126:406-8.
68. Akdis CA, Akdis M. Mechanisms of allergen-specific immunotherapy. J Allergy Clin Immunol 2011; 127:18-27.
69. Macaubas C, Wahlstrom J, Galvao da Silva AP et al. Allergen-specific MHC class II tetramer+ cells are detectable in allergic, but not in nonallergic, individuals. J Immunol 2006; 176:5069-77.
70. Van Overtvelt L, Wambre E, Maillere B et al. Assessment of Bet v 1-specific CD4+ T cell responses in allergic and nonallergic individuals using MHC class II peptide tetramers. J Immunol 2008; 180:4514-22.
71. Skrindo I, Farkas L, Kvale EO, Johansen FE, Jahnsen FL. Depletion of CD4+CD25+CD127lo regulatory T cells does not increase allergen-driven T cell activation. Clin Exp Allergy 2008; 38:1752-9.
72. Möbs C, Slotosch C, Löffler H, Jakob T, Hertl M, Pfützner W. Birch pollen immunotherapy leads to differential induction of regulatory T cells and delayed helper T cell immune deviation. J Immunol 2010; 184:2194-203.
73. 142-156 is the dominant T-cell epitope of the major birch pollen allergen and important for cross-reactivity with Bet v 1-related food allergens. J Allergy Clin Immunol 2005; 116:213-9.
74. Jahn-Schmid B, Wopfner N, Hubinger G et al. The T-cell response to Amb a 1 is characterized by 3 dominant epitopes and multiple MHC restriction elements. J Allergy Clin Immunol 2010; 126:1068-71.
75. Kinnunen T, Buhot C, Närvänen A et al. The immunodominant epitope of lipocalin allergen Bos d 2 is suboptimal for human T cells. Eur J Immunol 2003; 33:1717-26.
76. Juntunen R, Liukko A, Taivainen A et al. Suboptimal recognition of a T cell epitope of the major dog allergen Can f 1 by human T cells. Mol Immunol 2009; 46:3320-7.
77. Kinnunen T, Kwok WW, Närvänen A et al. Immunomodulatory potential of heteroclitic analogs of the dominant T-cell epitope of lipocalin allergen Bos d 2 on specific T cells. Int Immunol 2005; 17:1573-81.
78. Kinnunen T, Jutila K, Kwok WW et al. Potential of an altered peptide ligand of lipocalin allergen Bos d 2 for peptide immunotherapy. J Allergy Clin Immunol 2007; 119:965-72.
79. Saarelainen S, Kinnunen T, Buhot C et al. Immunotherapeutic potential of the immunodominant T-cell epitope of lipocalin allergen Bos d 2 and its analogs. Immunology 2008; 123:358-66.
80. Immonen A, Taivainen A, Närvänen A et al. Use of multiple peptides containing T cell epitopes is a feasible approach for peptide-based immunotherapy in Can f 1 allergy. Immunology 2007; 120:38-46.
81. Cai G, Hafler D. Multispecific responses by T cells expanded by endogenous self-peptide/MHC complexes. Eur J Immunol 2007; 37:602-12.
82. Zhang X, Tang Y, Sujkowska D et al. Degenerate TCR recognition and dual DR2 restriction of autoreactive T cells: implications for the initiation of the autoimmune response in multiple sclerosis. Eur J Immunol 2008; 38:1297-309.
83. Bateman EA, Ardern-Jones MR, Ogg GS. Persistent central memory phenotype of circulating Fel d 1 peptide/DRB1*0101 tetramer-binding CD4+ T cells. J Allergy Clin Immunol 2006; 118:1350-6.
84. Kinnunen T, Nieminen A, Kwok WW et al. Allergen-specific CD4+ T cells of memory and naive origin exhibit functional and phenotypic differences between allergic and nonallergic subjects. Eur J Immunol 2010; 40:2460-9.
85. Turner SJ, La Gruta NL, Kedzierska K, Thomas PG, Doherty PC. Functional implications of T cell receptor diversity. Curr Opin Immunol 2009; 21:286-90.
86. Reichstetter S, Ettinger RA, Liu AW, Gebe JA, Nepom GT, Kwok WW. Distinct T cell interactions with HLA class II tetramers characterize a spectrum of TCR affinities in the human antigen-specific T cell response. J Immunol 2000; 165:6994-8.
87. Gebe JA, Falk BA, Rock KA et al. Low-avidity recognition by CD4+ T cells directed to self-antigens. Eur J Immunol 2003; 33:1409-17.
88. Virtanen T, Zeiler T, Rautiainen J, Mäntyjärvi R. Allergy to lipocalins: a consequence of misguided T-cell recognition of self and nonself? Immunol Today 1999; 20:398-400.
89. Pfeiffer C, Stein J, Southwood S, Ketelaar H, Sette A, Bottomly K. Altered peptide ligands can control CD4 T lymphocyte differentiation in vivo. J Exp Med 1995; 181:1569-74.
90. Constant S, Pfeiffer C, Woodard A, Pasqualini T, Bottomly K. Extent of T cell receptor ligation can determine the functional differentiation of naive CD4+ T cells. J Exp Med 1995; 182:1591-6.
91. Hosken NA, Shibuya K, Heath AW, Murphy KM, O'Garra A. The effect of antigen dose on CD4+ T helper cell phenotype development in a T cell receptor-alpha beta-transgenic model. J Exp Med 1995; 182:1579-84.
92. Schountz T, Kasselman JP, Martinson FA, Brown L, Murray JS. MHC genotype controls the capacity of ligand density to switch T helper (Th)-1/Th-2 priming in vivo. J Immunol 1996; 157:3893-901.
93. + T cells by antigenic peptides altered for TCR binding. J Immunol 1997; 158:4237-44.
94. Rogers PR, Croft M. Peptide dose, affinity, and time of differentiation can contribute to the Th1/Th2 cytokine balance. J Immunol 1999; 163:1205-13.
95. Leitenberg D, Bottomly K. Regulation of naive T cell differentiation by varying the potency of TCR signal transduction. Semin Immunol 1999; 11:283-92.
96. Janssen EM, van Oosterhout AJM, van Rensen AJML, van Eden W, Nijkamp FP, Wauben MHM. Modulation of Th2 responses by peptide analogues in a murine model of allergic asthma: amelioration or deterioration of the disease process depends on the Th1 or Th2 skewing characteristics of the therapeutic peptide. J Immunol 2000; 164:580-8.
97. Brogdon JL, Leitenberg D, Bottomly K. The potency of TCR signaling differentially regulates NFATc/p activity and early IL-4 transcription in naive CD4+ T cells. J Immunol 2002; 168:3825-32.
98. Jenkins MK, Chu HH, McLachlan JB, Moon JJ. On the composition of the preimmune repertoire of T cells specific for peptide-major histocompatibility complex ligands. Annu Rev Immunol 2010; 28:275-94.
99. Moon JJ, Chu HH, Pepper M et al. Naive CD4(+) T cell frequency varies for different epitopes and predicts repertoire diversity and response magnitude. Immunity 2007; 27:203-13.
100. Obar JJ, Khanna KM, Lefrançois L. Endogenous naive CD8+ T cell precursor frequency regulates primary and memory responses to infection. Immunity 2008; 28:859-69.
101. Kotturi MF, Scott I, Wolfe T et al. Naive precursor frequencies and MHC binding rather than the degree of epitope diversity shape CD8+ T cell immunodominance. J Immunol 2008; 181:2124-33.
102. Milner JD, Fazilleau N, McHeyzer-Williams M, Paul W. Cutting Edge: lack of high affinity competition for peptide in polyclonal CD4+ responses unmasks IL-4 production. J Immunol 2010; 184:6569-73.
103. Platts-Mills T, Vaughan J, Squillace S, Woodfolk J, Sporik R. Sensitisation, asthma, and a modified Th2 response in children exposed to cat allergen: a population-based cross-sectional study. Lancet 2001; 357:752-6.
104. Ownby DR, Johnson CC, Peterson EL. Exposure to dogs and cats in the first year of life and risk of allergic sensitization at 6 to 7 years of age. JAMA 2002; 288:963-72.
105. Jeal H, Draper A, Harris J, Taylor AN, Cullinan P, Jones M. Modified Th2 responses at high-dose exposures to allergen: using an occupational model. Am J Respir Crit Care Med 2006; 174:21-5.
106. Tovey ER, Almqvist C, Li Q, Crisafulli D, Marks GB. Nonlinear relationship of mite allergen exposure to mite sensitization and asthma in a birth cohort. J Allergy Clin Immunol 2008; 122:114-8.
107. Riedl MA, Landaw EM, Saxon A, Diaz-Sanchez D. Initial high-dose nasal allergen exposure prevents allergic sensitization to a neoantigen. J Immunol 2005; 174:7440-5.
108. Emanuelsson C, Spangfort MD. Allergens as eukaryotic proteins lacking bacterial homologues. Mol Immunol 2007; 44:3256-60.
109. Jenkins JA, Breiteneder H, Mills EN. Evolutionary distance from human homologs reflects allergenicity of animal food proteins. J Allergy Clin Immunol 2007; 120:1399-405.
110. Virtanen T, Zeiler T, Mäntyjärvi R. Important animal allergens are lipocalin proteins: Why are they allergenic? Int Arch Allergy Immunol 1999; 120:247-58.
111. Virtanen T, Kinnunen T. Adaptive immunity as a determinant of allergenicity. J Allergy Clin Immunol 2009; 124:171-2.