Sequence comparisons of the CDR3 hyper-variable loops of human T cell receptors specific for three major T cell epitopes of the birch pollen allergen Bet v 1.
We have analysed the T cell receptor (TCR) alpha and beta chain sequences of 16 human CD4+ T cell clones (TCCs) specific for three important epitopes of the major birch pollen allergen Bet v 1. The TCCs were raised from the peripheral blood of eight patients with birch pollen allergy, showing allergic rhino-conjunctivitis and allergic asthma. The TCCs from these individuals were specific for Bet v 1-derived peptides: amino acids (aa)77-92 (epitope 1), aa93-108 (epitope 2) and aa113-126 (epitope 3). The DNA sequence analysis of the TCRAV and BV regions revealed heterogeneous repertoires for recognition of the peptides. Multiple combinations of AV/AJ and BV/BJ were used. However, some inter-individual restriction was evident. A limited selection of AVS and the normally infrequently used BV1S4 was obvious in TCCs specific for epitope 1. The TCRBV13 was more frequent in TCCs recognizing epitope 3. A very narrow distribution in length could be seen in the CDR3 sequences of the beta chain of TCRs with specificity for epitopes 1 and 2. Inter-individual positional micro-restriction was observed for the aa motif LR in the tCDR3 (epitope 1), for the aa residue M in the alphaCDR3 and for the aa residue G in the betaCDR3 (epitope 3). Our results illustrate clearly that each antigenic peptide derived from a single allergen, is capable of selecting different characteristics in the responding repertoire of TCRs, thus increasing the complexity of allergen-recognition by T lymphocytes. Therefore, our findings limit the potential use of TCR targeted therapeutical strategies in Type I allergy.
Breiteneder
H
H
Department of General and Experimental Pathology, University of Vienna, Austria. Heimo.Breiteneder@akh-wien.ac.at
Friedl-Hajek
R
R
Ebner
C
C
Schenk
S
S
Fischer
G
G
Kraft
D
D
Scheiner
O
O
D000485:Allergens / Q000276:immunology*; D000595:Amino Acid Sequence; D052179:Antigens, Plant; D001483:Base Sequence; D002999:Clone Cells; D003001:Cloning, Molecular; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D008297:Male; D008969:Molecular Sequence Data; D010940:Plant Proteins / Q000276:immunology*; D011058:Pollen / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D014197:Trees
D000485:Allergens; D052179:Antigens, Plant; D000939:Epitopes; D010940:Plant Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C061312:Bet v 1 allergen, Betula