Identification and characterization of autoreactive T cell responses to bullous pemphigoid antigen 2 in patients and healthy controls.
Antibodies against the extracellular domain of bullous pemphigoid antigen 2 (BPAG2) are thought to play a key role in the pathogenesis of bullous pemphigoid (BP), the most frequent autoimmune bullous disease of the skin. Autoreactive T cell responses to BPAG2 were investigated in 16 BP patients and 24 healthy controls by coculture of PBMC with two recombinant BPAG2 proteins (extracellular domain of BPAG2). Primary in vitro T cell responses to BPAG2 were observed in 10/12 BP patients expressing the BP-associated HLA-DQB1*0301 allele and 8/10 DQB1*0301 positive healthy individuals. DQB1*0301 also restricted three autoreactive T cell lines from two BP patients and a healthy donor. In contrast, PBMC from 14 normal patients carrying HLA class II alleles other than DQB1*0301 were not stimulated by BPAG2. Autoreactive BPAG2-specific CD4(+) T cell lines and clones from five BP patients produced both Th1 and Th2 cytokines, whereas three autoreactive T cell lines from three DQB1*0301 positive normal patients produced exclusively IFN-gamma. The absence of BPAG2-specific Th2 cells in healthy individuals strongly suggests that autoreactive Th2 responses to BPAG2 are restricted to BP patients and may thus be critical in the pathogenesis of BP.
Büdinger
L
L
Hautklinik, Universitätsklinikum der RWTH Aachen, D-52074 Aachen, Germany.
Borradori
L
L
Yee
C
C
Eming
R
R
Ferencik
S
S
Grosse-Wilde
H
H
Merk
H F
HF
Yancey
K
K
Hertl
M
M
D000328:Adult; D000368:Aged; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002352:Carrier Proteins; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D002999:Clone Cells / Q000276:immunology; D003094:Collagen / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D003598:Cytoskeletal Proteins; D000071821:Dystonin; D005434:Flow Cytometry; D006683:HLA-DQ Antigens / Q000276:immunology; D059866:HLA-DQ beta-Chains; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D010391:Pemphigoid, Bullous / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D012867:Skin / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D000097805:Collagen Type XVII
D001324:Autoantigens; D002352:Carrier Proteins; D003094:Collagen; D016207:Cytokines; D003598:Cytoskeletal Proteins; D000071821:Dystonin; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; D000949:Histocompatibility Antigens Class II; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D011994:Recombinant Proteins; D000097805:Collagen Type XVII; C486268:DST protein, human; C069051:HLA-DQB1 antigen