Distinct human T cell repertoires mediate immediate and delayed-type hypersensitivity to the Trichophyton antigen, Tri r 2.
The 29-kDa subtilase homologue, Tri r 2, derived from the dermatophyte fungus Trichophyton rubrum, exhibits unique immunologic characteristics in its ability to elicit immediate (IH) and delayed-type (DTH) hypersensitivity skin tests in different individuals. Thus, Tri r 2 provides a model for comparing the T cell repertoire in subjects with distinct immune responses to a single Ag. Recombinant Tri r 2 produced as a GST fusion protein in Escherichia coli stimulated strong in vitro lymphoproliferative responses in 10 IH and 10 DTH responders. Patterns of T cell epitope recognition were compared between skin test groups using 28 overlapping peptides (each in 12 replicate wells) derived from Tri r 2 to stimulate T lymphocyte proliferation in vitro. Peptide 5 (P5; aa 41-60) induced the strongest response in DTH subjects and showed the largest difference between DTH and IH responders in proliferation (mean standardized index, 2.22 and 0.82, respectively; p = 0.0047) and number of positive wells (81 vs 12). Responses to P5 were associated with diverse HLA haplotypes. These results showed that P5 contains an immunodominant epitope specifically associated with DTH and that this peptide is recognized in a permissive manner. Cross-validated linear discriminant analysis using T cell proliferative responses to two regions of Tri r 2 (aa 51-90 and 231-270) gave a 95% predictive accuracy for classification of subjects into IH or DTH groups. We conclude that different immune responses to Trichophyton are mediated by distinct T cell repertoires between individuals with IH and DTH reactions to Tri r 2.
Woodfolk
J A
JA
Asthma and Allergic Diseases Center, Department of Internal Medicine, University of Virginia, Charlottesville, VA 22908, USA. jaw4m@virginia.edu
Sung
S S
SS
Benjamin
D C
DC
Lee
J K
JK
Platts-Mills
T A
TA
D000328:Adult; D000368:Aged; D000485:Allergens / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D000595:Amino Acid Sequence; D000908:Antibodies, Fungal / Q000378:metabolism; D000946:Antigens, Fungal / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D001666:Binding Sites, Antibody; D002478:Cells, Cultured; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology; D005260:Female; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014249:Trichophyton / Q000276:immunology*
D000485:Allergens; D000908:Antibodies, Fungal; D000946:Antigens, Fungal; D018984:Epitopes, T-Lymphocyte; D005656:Fungal Proteins; D016056:Immunodominant Epitopes; D010455:Peptides; D011994:Recombinant Proteins; C115630:Tri r 2 allergen