DIVERSITY OF TCRAV AND TCRBV SEQUENCES USED BY HUMAN T-CELL CLONES SPECIFIC FOR A MINIMAL EPITOPE OF BET-V-1, THE MAJOR BIRCH POLLEN ALLERGEN

T-cell clones (TCC) were raised from the peripheral blood of patients suffering from tree pollen allergy. All TCC were restricted by HLA-DR molecules. In order to investigate possible intervention targets in Ty pe I allergic diseases, we examined T-cell receptor (TCR) alpha and be ta chain nucleotide sequences of five allergen-reactive human CD4(+) T CC specific for a C-terminal epitope (BV 144) of Bet v 1, the major bi rch pollen allergen. Proliferation assays using synthetic peptides rev ealed the 10-mer LRAVESYLLA as minimal epitope for three TCC; two TCC also displayed reactivity with the nonapeptide LRAVESYLL. Two TCC expr essed TCRBV2S3, all other BV144-specific TCC used diverse TCRAV and TC RBV gene segments. Moreover, the junctional regions encoding the third complementary determining regions (CDR3) of the TCR showed a striking heterogeneity in length and amino acid composition. Nevertheless, all TCC showed an arginine residue in the N-terminal region of their TCRB V CDR3 loops. Therefore therapeutical strategies aimed at the clonal d eletion of allergen-specific T-cell clones, providing help for IgE syn thesis, will not be feasible. Our results cast a doubt on the theory t hat the CDR3 exclusively provides the primary contact with the peptide bound in the major histocompatibility (MHC) groove, and suggest addit ional interaction with MHC class II.