1. Historical overview Pr G. Pauli Hôpitaux Universitaires de Strasbourg Bischenberg 21 septembre 2007

2. Allergens and allergic diseases

3. In the 70 ies *Allergenic sources were studied using electrophoretical methods (IEF, SDS-Page gel, crossed immunoelectrophoresis). In the early 80 ies *IgE responses against different components were determined (immunoblotting) Peltre G, Lapeyre J, David B. A nitrocellulose immunoprint technique to detect human antibodies to allergen extracts. JACI 1982 (1)

4. Since the 90 ies *Purification of allergenic proteins, determination of peptide sequences, use of monoclonal antibody technology (by immunization of mice with purified allergens). *Use of DNA technology for characterization and production of recombinant allergens (now the choice method). (2)

5. Some important dates (1) *1988 : cDNA cloning of Der p 1 (Dermatophagoïdes pteronyssinus). Chua et al. - J Exp Med *1988 : cDNA cloning of white-face hornet venom allergen. Fang et al. - PNSA *1989 : cDNA cloning of Bet v 1 (Birch). Breiteneder H et al. - Embo J

6. Some important dates (2) *1991 : cDNA cloning of profilin (a plant panallergen) Valenta R et al. - Science *1993 : cDNA cloning of Phl p 5 (grass : Phleum pratense). Vrtala S et al. - J of Immunology *1993 : cDNA cloning of Sin a 1 (yellow mustard). First food allergen to be cloned. Gonzales de la Pena, Villalba M et al. - Biochem Biophys Res Commun

7. Over the past 15 years the applications of rec DNA technology to allergens have exploded *Characterization of 569 allergenic molecules listed in Allergome (data bank of www.allergens.org) updated July 2007. *Numerous basic research studies (T cell epitope mapping, identification of three dimensional structures, IgE epitope mapping), production of allergen derivatives with reduced IgE binding capacity (hypoallergens).

8. Since the 90 ies Demonstration of biological in vivo activity of rec. allergens *By skin tests  Moser et al., r Asp f 1 J Immunol 1992 Aspergillus  Menz et al., r Bet v 1 Clin Exp Allergy 1996 Birch  Pauli et al., r Bet v 1JACI 1996 Birch r Bet v 2  Heiss et al., r Phl p 1,2,5J Investig Dermatol 1999 Grass Prick-tests (1 - 100 µg/ml). *By provocation tests  Bronchial : Godnic - Cvar et al, rBet v 1, JACI 1997  Nasal : Ruoppi et al., Bos d 2, Clin Exp Allergy 2001 Van Hage Hamsten et al., Bet v 1, Clin Exp Allergy 2002  Conjunctival : Arquint et al., rBet v 1, JACI 1999

9. More recently (21 st Cy) *Immunotherapy with recombinant allergens and recombinant hypoallergenic derivatives  demonstration of de novo IgG antibody responses against rec. allergens,  clinical results of phase 2 are available for 3 studies.

10. For the clinician (1) *Learning the importance of molecular allergens involved in allergic diseases Example for grass pollens (given by M. Hrabina, Stallergènes, France) Groupe 1 5 7 2/3 Groupe 10 Groupe 4 Groupe 12 Groupe 11 50% 40% Groupe 13 Low potential High potential % of specific IgE to individual molecular allergens Prevalence of sensitization

11. For the clinician (2) *Better identification of cross reactivities thanks to the repertory of molecular allergens  between respiratory allergens,  between food allergens,  between respiratory and food allergens. *New approaches towards allergy vaccinations.