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

Mol Immunol. 1996 Sep;33(13):1039-48. doi: 10.1016/s0161-5890(96)00064-8.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Allergens / immunology*
  • Amino Acid Sequence
  • Antigens, Plant
  • Base Sequence
  • Clone Cells
  • Cloning, Molecular
  • Epitope Mapping
  • Epitopes / immunology*
  • Female
  • Humans
  • Hypersensitivity / immunology*
  • Male
  • Molecular Sequence Data
  • Plant Proteins / immunology*
  • Pollen / immunology*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics*
  • Sequence Analysis, DNA
  • Sequence Homology
  • Trees

Substances

  • Allergens
  • Antigens, Plant
  • Epitopes
  • Plant Proteins
  • Receptors, Antigen, T-Cell, alpha-beta
  • Bet v 1 allergen, Betula

Associated data

  • GENBANK/X92875
  • GENBANK/X92876
  • GENBANK/X92877
  • GENBANK/X92878
  • GENBANK/X92879
  • GENBANK/X92880
  • GENBANK/X92881
  • GENBANK/X92882
  • GENBANK/X92883
  • GENBANK/X92884
  • GENBANK/X92885