title: Identification of HLA-DR-bound peptides presented by human bronchoalveolar lavage cells in sarcoidosis.
abstract: Sarcoidosis is an inflammatory disease of unknown etiology, most commonly affecting the lungs. Activated CD4+ T cells accumulate in the lungs of individuals with sarcoidosis and are considered to be of central importance for inflammation. We have previously shown that Scandinavian sarcoidosis patients expressing the HLA-DR allele DRB1*0301 are characterized by large accumulations in the lungs of CD4+ T cells expressing the TCR AV2S3 gene segment. This association afforded us a unique opportunity to identify a sarcoidosis-specific antigen recognized by AV2S3+ T cells. To identify candidates for the postulated sarcoidosis-specific antigen, lung cells from 16 HLA-DRB1*0301pos patients were obtained by bronchoalveolar lavage. HLA-DR molecules were affinity purified and bound peptides acid eluted. Subsequently, peptides were separated by reversed-phase HPLC and analyzed by liquid chromatography-mass spectrometry. We identified 78 amino acid sequences from self proteins presented in the lungs of sarcoidosis patients, some of which were well-known autoantigens such as vimentin and ATP synthase. For the first time, to our knowledge, we have identified HLA-bound peptides presented in vivo during an inflammatory condition. This approach can be extended to characterize HLA-bound peptides in various autoimmune settings.
authors.affiliation: Lung Research Laboratory, Department of Medicine, Karolinska Institutet, Stockholm, Sweden. jan.wahlstrom@ki.se
authors.forename: Jan
authors.initials: J
authors.lastname: Wahlström
authors.forename: Jörn
authors.initials: J
authors.lastname: Dengjel
authors.forename: Bengt
authors.initials: B
authors.lastname: Persson
authors.forename: Hüseyin
authors.initials: H
authors.lastname: Duyar
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Rammensee
authors.forename: Stefan
authors.initials: S
authors.lastname: Stevanović
authors.forename: Anders
authors.initials: A
authors.lastname: Eklund
authors.forename: Robert
authors.initials: R
authors.lastname: Weissert
authors.forename: Johan
authors.initials: J
authors.lastname: Grunewald
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D005260:Female; D006684:HLA-DR Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017565:Sarcoidosis, Pulmonary / Q000235:genetics / Q000276:immunology* / Q000473:pathology
chemical_list: D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553502:HLA-DRB1*03:01 antigen; D010455:Peptides