Allergological implication of the quaternary hexameric structure of the cockroach allergen Per a 3.
BACKGROUND
Cockroach allergens play a very important role in allergic diseases, especially asthma. The major allergen of the American cockroach (Periplaneta americana), Per a 3, naturally occurs as isoforms of hexamers.


OBJECTIVE
The aim of this study was to investigate whether the hexameric structures of Per a 3 influence their allergenicity and immunogenicity.


METHODS
Therefore, we compared the different effects of native hexamers and dissociated monomers of cockroach haemolymph (HL), containing almost only Per a 3 proteins (HL-Per a 3), on proliferation and T-helper type 1 (Th1)/Th2 cytokine production of human CD4(+) T cells in co-culture with allergen-pulsed monocyte-derived autologous dendritic cells (DC) as well as the leukotriene release of basophils.


RESULTS
In P. americana-sensitized and non-sensitized donors the HL-Per a 3 monomers were internalized faster by immature DC and induced higher proliferation and IFN-gamma production than the hexamers. While in non-sensitized donors IL-4 and IL-5 as well as IL-10 production were also increased after stimulation with monomeric HL-Per a 3-pulsed DC, Th2 cytokine and IL-10 production were only enhanced in P. americana-sensitized donors using hexameric HL-Per a 3-pulsed DC. Furthermore, in the leukotriene release assay the monomers were less effective than the hexamers.


CONCLUSIONS
Our data indicate that the quaternary structure can influence both allergenicity and immunogenicity, also depending on the sensitization status. The monomeric variant of Per a 3 allergens could be a possible candidate for a specific immunotherapy because the IgE-mediated allergic reaction and the Th2-inducing capacity are diminished while the Th1-inducing capacity is retained.
Bellinghausen
I
I
Department of Dermatology, University of Mainz, Mainz, Germany. bellinghausen@hautklinik.klinik.uni-mainz.de
Häringer
B
B
Lafargue
B
B
Strand
D
D
König
B
B
Decker
H
H
Saloga
J
J
D000485:Allergens / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D001491:Basophils / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D003058:Cockroaches; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000378:metabolism; D004705:Endocytosis; D006458:Hemolymph / Q000737:chemistry / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000097:blood / Q000276:immunology*; D015289:Leukotrienes / Q000378:metabolism; D015394:Molecular Structure; D020836:Protein Structure, Quaternary; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism
D000485:Allergens; D016207:Cytokines; D015289:Leukotrienes; C511812:Per a 6 allergen, Periplaneta americana