Inhibition of human T-cell responses to house dust mite allergens by a T-cell receptor peptide.
Recent analysis of the usage of T-cell receptor (TcR) beta chain variable region (V beta) gene elements by house dust mite (HDM)-reactive T cells from an atopic donor suggested that TcR-V beta 3 gene products may form a major component of the human T-cell repertoire reactive to this common allergen. In this study a peptide analog of the TcR-V beta 3 complementarity determining region 2 (CDR2) is shown to inhibit the polyclonal human T-cell response to HDM; this effect is specific because inhibition is dependent on the presence of V beta 3 + T cells. This experimental approach has been used to determine whether the pattern seen in T-cell clones derived from one atopic donor reflects TcR-V beta usage in the polyclonal response to allergen in the general population. Inhibition of more than 50% of the polyclonal response to allergen by V beta 3-CDR2 peptide was observed in 16 of 21 donors tested, suggesting that TcR-V beta 3 gene usage may form a major component of the human HDM repertoire and as such offer a suitable target for T cell-directed specific immunotherapy in HDM-allergic individuals. Depletion of CD8+ T cells abolishes peptide-mediated inhibition of CD4+ T-cell proliferation to HDM, suggesting that induction of a CD8+ regulatory T-cell subset by the CDR2 peptide may modulate HDM-specific allergic T-cell responses.
Jarman
E R
ER
Department of Immunology, St Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, London.
Hawrylowicz
C M
CM
Panagiotopolou
E
E
O'Hehir
R E
RE
Lamb
J R
JR
D000485:Allergens / Q000276:immunology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D002999:Clone Cells; D004391:Dust; D006801:Humans; D008925:Mites / Q000276:immunology*; D010446:Peptide Fragments / Q000494:pharmacology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D000485:Allergens; D004391:Dust; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta