Molecular variability of group 1 and 5 grass pollen allergens between Pooideae species: implications for immunotherapy.
BACKGROUND
Differences between major allergens from distinct grass species remain to be investigated, both in terms of structure and antigenicity.


METHODS
Group 1 and 5 allergens purified from five common Pooideae species were analysed by mass spectrometry (MS). Major histocompatibility complex (MHC) class II-restricted T cell epitopes were identified using predictive algorithms and human leucocyte antigen (HLA)-binding assays. CD4+ T cell reactivity and IgE binding were assessed based on the induction of CD154 expression in peripheral blood mononuclear cells and using competitive ELISA assays, respectively.


RESULTS
MS analysis of group 5 pollen allergens reveals considerable intra- and inter-species variability in amino acid sequence, with 30-50 predominant isoforms found for each species. Differences in the amino acid sequence as well as N- and O-glycosylation contribute to the variability of group 1 allergens, yielding 5-10 main isoforms, depending on the species. Out of 14 MHC class II-restricted T cell epitopes identified within group 1, only one is conserved among the five grass species. Significant differences in binding affinities for HLA-DR molecules result in variable CD4+ T cell recognition of group 1 and 5 allergens purified from the various species. Up to 38% and 85% of patients exhibit seric IgE responses to species-restricted (or semi-restricted) epitopes associated with group 1 or 5 allergens, respectively.


CONCLUSIONS
Major pollen allergens from distinct grass species bear both shared and species-restricted T and B cell immune epitopes. When compared with single extracts, a five grass pollen extract is thus more suitable for specific immunotherapy, as it contains a broader repertoire of the IgE epitopes to which patients are sensitized.
Chabre
H
H
Stallergenes SA, 6 rue Alexis de Tocqueville, 92160 Antony, France.
Gouyon
B
B
Huet
A
A
Baron-Bodo
V
V
Boran-Bodo
V
V
Nony
E
E
Hrabina
M
M
Fenaille
F
F
Lautrette
A
A
Bonvalet
M
M
Maillère
B
B
Bordas-Le Floch
V
V
Van Overtvelt
L
L
Jain
K
K
Ezan
E
E
Batard
T
T
Moingeon
P
P
D000485:Allergens / Q000737:chemistry* / Q000145:classification* / Q000276:immunology / Q000302:isolation & purification; D000595:Amino Acid Sequence; D000818:Animals; D000937:Antigen-Antibody Reactions; D003888:Desensitization, Immunologic; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007962:Leukocytes / Q000276:immunology; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010449:Peptide Mapping; D006109:Poaceae / Q000737:chemistry* / Q000145:classification*; D011058:Pollen / Q000737:chemistry*; D011487:Protein Conformation; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology
D000485:Allergens; D000939:Epitopes; D007073:Immunoglobulin E