Vbeta18.1(+) and V(alpha)2.3(+) T-cell subsets are associated with house dust mite allergy in human subjects.
BACKGROUND
The recognition of allergenic peptides by T cells through their T-cell receptor (TCR) represents a crucial step in the initiation of an allergen-specific immune response. In parallel to the superantigen-driven restricted expansion of Vbeta subsets in autoimmune and infectious diseases, reports in animals and human subjects have shown a similar capacity of classical antigens.


OBJECTIVE
The study was performed to analyze the V(alpha)/Vbeta expression in house dust mite (HDM) allergy.


METHODS
The TCR repertoire of 15 subjects with HDM allergy, 22 atopic subjects without HDM allergy, and 19 nonatopic individuals, members of 2 extended and 4 nuclear families, was determined. By using flow cytometry, the expression of 22 Vbeta and 3 V(alpha) elements was analyzed in vivo and after in vitro allergen stimulation.


RESULTS
In comparison with nonatopic and atopic individuals without HDM allergy, freshly isolated PBMCs of individuals with HDM allergy showed a significantly higher frequency of Vbeta18(+) and V(alpha)2.3(+) T cells. Although members of all 3 groups had a similar lymphocyte proliferation response after in vitro stimulation with Der p 1 or Der p 1 peptide(101-131), a significant expansion of Vbeta18(+) and V(alpha)2.3(+) T cells in vitro occurred only in individuals with HDM allergy. Moreover, the degree of expansion correlated with the levels of allergen-specific IgE antibodies. No expansion of Vbeta18(+) and V(alpha)2.3(+) was observed after mitogen stimulation with PHA, indicating allergen specificity of the response.


CONCLUSIONS
Our results strongly suggest restricted TCR V(alpha)/Vbeta gene use in HDM allergy and might be a step toward TCR-based immunotherapy.
Kircher
Moritz F
MF
Institute of Clinical Chemistry and Biochemistry, Berlin, Germany.
Haeusler
Tom
T
Nickel
Renate
R
Lamb
Jonathan R
JR
Renz
Harald
H
Beyer
Kirsten
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D039741:Antigens, Dermatophagoides; D002648:Child; D002675:Child, Preschool; D004391:Dust / Q000009:adverse effects*; D005260:Female; D005434:Flow Cytometry; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D008925:Mites / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D039741:Antigens, Dermatophagoides; D004391:Dust; D006023:Glycoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta