title: Previously undescribed grass pollen antigens are the major inducers of T helper 2 cytokine-producing T cells in allergic individuals.
abstract: T cells play an important role in the pathogenesis of allergic diseases. However, the proteins considered as potential immunogens of allergenic T-cell responses have traditionally been limited to those that induce IgE responses. Timothy grass (TG) pollen is a well-studied inhaled allergen for which major IgE-reactive allergens have also been shown to trigger T helper 2 (Th2) responses. Here we examined whether other TG pollen proteins are recognized by Th2 responses independently of IgE reactivity. A TG pollen extract was analyzed by 2D gel electrophoresis and IgE/IgG immunoblots using pooled sera from allergic donors. Mass spectrometry of selected protein spots in combination with de novo sequencing of the whole TG pollen transcriptome identified 93 previously undescribed proteins for further study, 64 of which were not targeted by IgE. Predicted MHC binding peptides from the previoulsy undescribed TG proteins were screened for T-cell reactivity in peripheral blood mononuclear cells from allergic donors. Strong IL-5 production was detected in response to peptides from several of the previously undescribed proteins, most of which were not targeted by IgE. Responses against the dominant undescribed epitopes were associated with the memory T-cell subset and could even be detected directly ex vivo after Th2 cell enrichment. These findings demonstrate that a combined unbiased transcriptomic, proteomic, and immunomic approach identifies a greatly broadened repertoire of protein antigens targeted by T cells involved in allergy pathogenesis. The discovery of proteins that induce Th2 cells but are not IgE reactive may allow the development of safer immunotherapeutic strategies.
authors: La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
authors: Véronique
authors: V
authors: Schulten
authors: Jason A
authors: JA
authors: Greenbaum
authors: Michael
authors: M
authors: Hauser
authors: Denise M
authors: DM
authors: McKinney
authors: John
authors: J
authors: Sidney
authors: Ravi
authors: R
authors: Kolla
authors: Cecilia S
authors: CS
authors: Lindestam Arlehamn
authors: Carla
authors: C
authors: Oseroff
authors: Rapheul
authors: R
authors: Alam
authors: David H
authors: DH
authors: Broide
authors: Fatima
authors: F
authors: Ferreira
authors: Fatima
authors: F
authors: Ferreira-Briza
authors: Howard M
authors: HM
authors: Grey
authors: Alessandro
authors: A
authors: Sette
authors: Bjoern
authors: B
authors: Peters
mesh_terms: D000485:Allergens / Q000276:immunology; D000906:Antibodies / Q000276:immunology; D052179:Antigens, Plant / Q000276:immunology*; D015180:Electrophoresis, Gel, Two-Dimensional; D000939:Epitopes / Q000276:immunology; D020869:Gene Expression Profiling; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology*; D015151:Immunoblotting; D007073:Immunoglobulin E / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology; D015848:Interleukin-5 / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D031784:Phleum / Q000276:immunology*; D010936:Plant Extracts / Q000276:immunology; D010940:Plant Proteins / Q000276:immunology; D011058:Pollen / Q000276:immunology*; D040901:Proteomics; D018418:Th2 Cells / Q000276:immunology*; D014019:Tissue Donors
chemical_list: D000485:Allergens; D000906:Antibodies; D052179:Antigens, Plant; D000939:Epitopes; D015848:Interleukin-5; D010936:Plant Extracts; D010940:Plant Proteins; D007073:Immunoglobulin E
references: PLoS One. 2011 Mar 15;6(3):e17712
references: 21423609
references: Allergy Asthma Proc. 2007 Jan-Feb;28(1):3-9
references: 17390749
references: Clin Allergy Immunol. 2008;21:47-58
references: 18828497
references: J Immunol. 2010 Jul 15;185(2):943-55
references: 20554959
references: J Allergy Clin Immunol. 2000 Mar;105(3):399-408
references: 10719286
references: J Immunol. 2012 Jul 15;189(2):679-88
references: 22706084
references: J Autoimmun. 1989 Jun;2 Suppl:45-53
references: 2570591
references: J Allergy Clin Immunol. 2010 Sep;126(3):466-76
references: 20816182
references: Regul Toxicol Pharmacol. 2011 Dec;61(3):365-72
references: 22019813
references: Expert Opin Investig Drugs. 2000 Mar;9(3):515-27
references: 11060692
references: Nature. 1985 Apr 11-17;314(6011):537-9
references: 3157869
references: J Immunol. 2012 Aug 15;189(4):1800-11
references: 22786768
references: Eur Respir J. 2004 Nov;24(5):758-64
references: 15516669
references: Immunity. 2008 Jun;28(6):847-58
references: 18549802
references: Allergol Immunopathol (Madr). 2001 Jan-Feb;29(1):9-15
references: 11449535
references: BMC Bioinformatics. 2010 Nov 22;11:568
references: 21092157
references: Eur J Immunol. 2000 May;30(5):1255-62
references: 10820370
references: Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1344-9
references: 9037055
references: Prog Allergy. 1978;25:1-62
references: 362426
references: PLoS Comput Biol. 2008 Apr 04;4(4):e1000048
references: 18389056
references: Clin Immunol. 2006 Jul;120(1):45-56
references: 16473552
references: Immunity. 2012 Feb 24;36(2):175-87
references: 22326582
references: Allergy. 2009 Mar;64(3):452-60
references: 19170672
references: J Allergy Clin Immunol. 2007 Feb;119(2):384-90
references: 17291855
references: Clin Exp Allergy. 1998 Mar;28(3):315-21
references: 9543081
references: J Allergy Clin Immunol. 2008 Dec;122(6):1154-60
references: 18951617
references: J Allergy Clin Immunol. 1998 Feb;101(2 Pt 1):241-9
references: 9500758
references: Curr Opin Allergy Clin Immunol. 2004 Aug;4(4):313-8
references: 15238798
references: Genome Res. 2008 May;18(5):821-9
references: 18349386
references: Clin Invest Med. 1996 Dec;19(6):461-9
references: 8959356
references: Int Arch Allergy Immunol. 2003 Feb;130(2):87-107
references: 12673063
references: Immunol Lett. 2010 May 4;130(1-2):57-65
references: 20004689