International Immunology, Vol. 11, No. 8, 1313-1326,
August 1999
© 1999 Japanese Society for Immunology
On the diversity and heterogeneity of H-2d-restricted determinants and T cell epitopes from the major bee venom allergen
Département d'Ingénierie et d'Etudes des Protéines, CEA-Saclay, 91191 Gif sur Yvette, France
Correspondence to: B. Maillère
One of the main limitations of using synthetic peptides for immunotherapy in allergic patients is the difficulty to delineate the immunodominant T cell epitopes which are necessarily dependent on HLA molecules. We have thus addressed the question of the role of MHC II molecules in immunodominant epitopes selection in the particular case of the major bee venom allergen (API m1). To exhaustively and easily explore it, we used BALB/c mice whose H-2 haplotype is associated with high IgE and IgG responses to API m1. By means of extensive sets of synthetic peptides, we investigated the specificity of polyclonal T cells and monoclonal hybridomas from mice immunized with API m1 and delineated four immunodominant regions, restricted to either the I-Ed or the I-Ad molecule. All the peptides were also tested for their capacity to bind to immunopurified MHC II molecules. Eight determinants of high affinity were identified. They clustered into three distinct regions and were largely overlapping. They included all the immunodominant epitopes, but half of them were not capable of stimulating T cells. Strikingly, interacting surfaces with either the TCR or MHC II molecule greatly differed from one determinant to another. In one case, we observed that flanking regions exerted a particular action on T cell stimulation which prevented the fine epitope localization. Our results underline the diversity and complexity of MHC II-restricted determinants and T cell epitopes from the major bee venom allergen, even in a single haplotype. These data also participate in the development of alternative approaches to conventional immunotherapy.
Keywords: allergy, antigen, antigen presentation, bee venom, epitope, MHC, peptide, phospholipase A2, T lymphocytes
1 Present address: LMIP, Université Paris-Sud, 91405 Orsay, France
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. M. Williams and E. C. Bigley III Identification of an I-Ed-Restricted T-Cell Epitope of Escherichia coli Outer Membrane Protein F Infect. Immun., July 1, 2004; 72(7): 3907 - 3913. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Chiari, G. Hames, V. Stroobant, C. Texier, B. Maillère, T. Boon, and P. G. Coulie Identification of a Tumor-specific Shared Antigen Derived From an Eph Receptor and Presented to CD4 T Cells on HLA Class II Molecules Cancer Res., September 1, 2000; 60(17): 4855 - 4863. [Abstract] [Full Text]
|
|
|
|
 |
|
 C. Texier, S. Pouvelle, M. Busson, M. Herve, D. Charron, A. Menez, and B. Maillere HLA-DR Restricted Peptide Candidates for Bee Venom Immunotherapy J. Immunol., March 15, 2000; 164(6): 3177 - 3184. [Abstract] [Full Text] [PDF]
|
|