Autoimmune T cell responses to antigenic peptides presented by bronchoalveolar lavage cell HLA-DR molecules in sarcoidosis.
The etiology of sarcoidosis remains unknown. Recently, by mass spectrometric sequencing of peptides eluted from HLA-DR molecules of bronchoalveolar lavage (BAL) cells from DRB10301(pos) patients, we identified potential self-antigens in sarcoidosis. The aim of the present study was to investigate the capacity of selected peptides to stimulate lung and blood T cells of sarcoidosis patients using an interferon-gamma ELISPOT assay. In peripheral blood, there were strong T cell responses to a peptide derived from the cytoskeletal protein vimentin in 6 out of 11 DRB10301(pos) patients with active disease but not in patients with other HLA types. BAL T cell responses against peptides derived from ATP synthase or from lysyl-tRNA synthetase were detected in DRB10301(pos) as well as DRB10301(neg) patients. By using antigenic peptides presented in vivo in the lungs of sarcoidosis patients, we have identified blood and lung T cell autoimmune responses that may help sustain the inflammation in this disease.
Karolinska Institutet, Department of Medicine, Lung Research Laboratory, L4:01, Karolinska University Hospital, Solna, 171 76 Stockholm, Sweden. jan.wahlstrom@ki.se
Jan
J
Wahlström
Jörn
J
Dengjel
Ola
O
Winqvist
Ira
I
Targoff
Bengt
B
Persson
Hüseyin
H
Duyar
Hans-Georg
HG
Rammensee
Anders
A
Eklund
Robert
R
Weissert
Johan
J
Grunewald
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000604:Amino Acyl-tRNA Synthetases / Q000276:immunology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology*; D001999:Bronchoscopy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology*; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D016133:Polymerase Chain Reaction; D017565:Sarcoidosis, Pulmonary / Q000097:blood / Q000276:immunology*; D018709:Statistics, Nonparametric; D014746:Vimentin / Q000276:immunology
D001323:Autoantibodies; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D010446:Peptide Fragments; D014746:Vimentin; D004247:DNA; D000604:Amino Acyl-tRNA Synthetases