In vivo clonal dominance and limited T-cell receptor usage in human CD4+ T-cell recognition of house dust mite allergens.
Sensitivity to house dust mite antigens in atopic individuals is a major cause of allergic diseases, ranging from asthma to rhinitis and dermatitis. We have studied the T-cell receptor (TCR) usage of house-dust-mite-specific CD4+ T-cell clones isolated from an atopic individual, by using the anchored polymerase chain reaction, and have analyzed the peripheral TCR repertoire of the same individual. Several T-cell clones had identified TCRs at the sequence level, despite the fact that they had been independently isolated, in some cases, in different years. These data suggest the presence in vivo of long-lived T-cell clones. We have also shown that junctional sequences identical to these clones are present in peripheral blood T cells taken 6 years after the isolation of the T-cell clones. The analysis of TCR genes used by the panel of clones reveals oligoclonality, with the variable (V) region gene segments V alpha 8 and V beta 3 being dominant, although there is minimal conservation of junctional sequences. The results have implications for understanding the TCR recognition of an environmental aeroallergen and the life span of T-cell clones in vivo during a chronic immune response.
Wedderburn
L R
LR
Imperial Cancer Research Fund, London, United Kingdom.
O'Hehir
R E
RE
Hewitt
C R
CR
Lamb
J R
JR
Owen
M J
MJ
D000485:Allergens / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D001483:Base Sequence; D015704:CD4 Antigens / Q000276:immunology*; D002999:Clone Cells; D004391:Dust; D006801:Humans; D008285:Major Histocompatibility Complex; D008925:Mites / Q000276:immunology*; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D015345:Oligonucleotide Probes; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis* / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic
D000485:Allergens; D015703:Antigens, CD; D015704:CD4 Antigens; D004391:Dust; D009838:Oligodeoxyribonucleotides; D015345:Oligonucleotide Probes; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta