Diversity of human T cell receptor sequences of T cell clones with specificity for Bet v 1 peptide/MHC II complexes.
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 have examined T cell receptor (TCR) alpha- and beta-chain nucleotide sequences of several allergen-reactive human CD4+ TCC specific for four frequently found epitopes of Bet v 1, the major birch pollen allergen. In general, TCC specific for the 4 epitopes investigated, used diverse TCRAV and TCRBV gene segments. Moreover, the junctional regions encoding the third complementarity determining regions (CDR3) of the TCR showed striking heterogeneities in length and amino acid composition. A more restricted use of two J gene segments (TCRBJ1S4 and 2S7) was only observed in the beta-chain of TCR used by TCC specific for epitope 1. In addition, all TCC specific for epitope 4 showed an arginine residue in the N-terminal region of their TCRBV CDR3 loops despite their sequence diversities. In view of the striking heterogeneities found, therapeutical strategies aimed at the clonal deletion of allergen-specific T cell clones, providing help for IgE synthesis, may not be feasible. Moreover, 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.
Hajek
R
R
Hüttinger
R
R
Ebner
C
C
Schenk
S
S
Kraft
D
D
Scheiner
O
O
D000485:Allergens / Q000276:immunology*; D000595:Amino Acid Sequence; D052179:Antigens, Plant; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002999:Clone Cells; D004247:DNA; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D014644:Genetic Variation; D006684:HLA-DR Antigens / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D010940:Plant Proteins / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D011994:Recombinant Proteins / Q000276:immunology
D000485:Allergens; D052179:Antigens, Plant; D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D010455:Peptides; D010940:Plant Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011994:Recombinant Proteins; C061312:Bet v 1 allergen, Betula; D004247:DNA