T-Cell epitopes and human leukocyte antigen restriction elements of an immunodominant antigen of Blastomyces dermatitidis.
Humans infected with the dimorphic fungus Blastomyces dermatitidis develop strong T-lymphocyte responses to WI-1, an immunodominant antigen that has been shown to elicit protective immunity in mice. In the present study, the T-cell epitopes of WI-1 and human leukocyte antigen (HLA) restricting elements that display them were investigated. Peripheral blood mononuclear cells (PBMC) from 37 patients with a confirmed history of blastomycosis were tested for a response to WI-1 in primary proliferation assays; PBMC from 35 (95%) responded. Six patients whose PBMC proliferated strongly in response to WI-1 (defined as a stimulation index greater than 50) were tested further for responses to subcloned, recombinant fragments of the antigen. These patients responded chiefly to sequences within the N terminus and the 25-amino-acid tandem repeat. Cloned CD4(+) T cells from an infected individual were used to delineate more precisely the peptide epitopes in the fragments and HLA restricting elements that present them. A majority of the T-cell clones recognized an epitope spanning amino acids 149 to 172 within the N terminus, displayed by HLA-DR 15. A minority of the clones, which have been shown to perform a cytolytic function in vitro, recognized an epitope in the tandem repeat displayed by HLA-DPw4, an uncommon restricting element. Tandem repeat epitopes required display by the beta chain of DPw4 heterodimers. Thus, human T cells with different functions in vitro also recognize distinct regions of WI-1, raising the possibility that HLA restricting elements that present them could modulate immunity during blastomycosis by selection and display of WI-1 peptides.
Chang
W L
WL
Department of Internal Medicine, Louisiana State University Medical School, Shreveport, Louisiana 71103, USA.
Audet
R G
RG
Aizenstein
B D
BD
Hogan
L H
LH
DeMars
R I
RI
Klein
B S
BS
D000595:Amino Acid Sequence; D000946:Antigens, Fungal / Q000276:immunology*; D001758:Blastomyces / Q000276:immunology*; D001759:Blastomycosis / Q000276:immunology; D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens / Q000502:physiology*; D006682:HLA-DP Antigens / Q000502:physiology; D006684:HLA-DR Antigens / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data
D000946:Antigens, Fungal; D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; D006682:HLA-DP Antigens; D006684:HLA-DR Antigens