TY - JOUR
T1 - Inhibition of human T-cell responses to house dust mite allergens by a T-cell receptor peptide
AU - Jarman, Elizabeth R.
AU - Hawrylowicz, Catherine M.
AU - Panagiotopolou, Elizabeth
AU - O'Hehir, Robyn E.
AU - Lamb, Jonathan R.
PY - 1994/1/1
Y1 - 1994/1/1
N2 - Recent analysis of the usage of T-cell receptor (TcR) β chain variable region (Vβ) gene elements by house dust mite (HDM)-reactive T cells from an atopic donor suggested that TcR-Vβ3 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-Vβ3 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 Vβ3 + 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-Vβ usage in the polyclonal response to allergen in the general population. Inhibition of more than 50% of the polyclonal response to allergen by Vβ3-CDR2 peptide was observed in 16 of 21 donors tested, suggesting that TcR-Vβ3 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.
AB - Recent analysis of the usage of T-cell receptor (TcR) β chain variable region (Vβ) gene elements by house dust mite (HDM)-reactive T cells from an atopic donor suggested that TcR-Vβ3 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-Vβ3 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 Vβ3 + 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-Vβ usage in the polyclonal response to allergen in the general population. Inhibition of more than 50% of the polyclonal response to allergen by Vβ3-CDR2 peptide was observed in 16 of 21 donors tested, suggesting that TcR-Vβ3 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.
KW - House dust mite
KW - T cells
KW - TcR-CDR2 peptide
UR - http://www.scopus.com/inward/record.url?scp=0028072311&partnerID=8YFLogxK
U2 - 10.1016/0091-6749(94)90152-X
DO - 10.1016/0091-6749(94)90152-X
M3 - Article
C2 - 7963153
AN - SCOPUS:0028072311
SN - 0091-6749
VL - 94
SP - 844
EP - 852
JO - The Journal of Allergy and Clinical Immunology
JF - The Journal of Allergy and Clinical Immunology
IS - 5
ER -