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 Type I allergic diseases, we examined T-cell receptor (TCR) alpha and beta chain nucleotide sequences of five allergen-reactive human CD4+ TCC specific for a C-terminal epitope (BV 144) of Bet v 1, the major birch pollen allergen. Proliferation assays using synthetic peptides revealed the 10-mer LRAVESYLLA as minimal epitope for three TCC; two TCC also displayed reactivity with the nonapeptide LRAVESYLL. Two TCC expressed TCRBV2S3, all other BV144-specific TCC used diverse TCRAV and TCRBV 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 TCRBV CDR3 loops. Therefore, therapeutical strategies aimed at the clonal deletion of allergen-specific T-cell clones, providing help for IgE synthesis, will not be feasible. Our results cast a doubt on the theory that the CDR3 exclusively provides the primary contact with the peptide bound in the major histocompatibility (MHC) groove, and suggest additional interaction with MHC class II.
Breiteneder
H
H
Institute of General and Experimental Pathology, University of Vienna, Austria.
Scheiner
O
O
Hajek
R
R
Hulla
W
W
Hüttinger
R
R
Fischer
G
G
Kraft
D
D
Ebner
C
C
D000485:Allergens / Q000276:immunology*; D000595:Amino Acid Sequence; D052179:Antigens, Plant; D001483:Base Sequence; D002999:Clone Cells; D018604:Epitope Mapping; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010940:Plant Proteins / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*
D000485:Allergens; D052179:Antigens, Plant; D010940:Plant Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C061312:Bet v 1 allergen, Betula