SEQUENCE COMPARISONS OF THE CDR3 HYPER-VARIABLE LOOPS OF HUMAN T-CELLRECEPTORS SPECIFIC FOR 3 MAJOR T-CELL EPITOPES OF THE BIRCH POLLEN ALLERGEN BET-V-1

We have analysed the T cell receptor (TCR) alpha and beta chain sequen ces 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 ra ised from the peripheral blood of eight patients with birch pollen all ergy, showing allergic rhino-conjunctivitis and allergic asthma. The T CCs 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 re vealed heterogeneous repertoires for recognition of the peptides. Mult iple combinations of AV/AJ and BV/BJ were used. However, some inter-in dividual restriction was evident. A limited selection of AV8 and the n ormally infrequently used BV1S4 was obvious in TCCs specific for epito pe 1. The TCRBV13 was more frequent in TCCs recognizing epitope 3. A v ery 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 beta CDR3 (epitope 1), for the aa residue M in the alpha CD R3 and for the aa residue G in the beta CDR3 (epitope 3). Our results illustrate clearly that each antigenic peptide derived from a single a llergen, is capable of selecting different characteristics in the resp onding repertoire of TCRs, thus increasing the complexity of allergen- recognition by T lymphocytes. Therefore, our findings limit the potent ial use of TCR targeted therapeutical strategies in Type I allergy. Co pyright (C) 1996 Elsevier Science Ltd.