Journal Article

Identification of HLA-DR–bound peptides presented by human bronchoalveolar lavage cells in sarcoidosis

Stevanoviδc, Stefan, Wahlström, Jan, Dengjel, Jörn, Rammensee, Hans-Georg, Eklund, Anders, Persson, Bengt, Duyar, Hüseyin, Weissert, Robert, Grunewald, Johan

2007

Overview

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.

• Publisher: American Society for Clinical Investigation
• Subject: Adult / Aged / Amino Acid Sequence / Amino acids / Antigens / Biomedical research / Bronchoalveolar Lavage Fluid - cytology / Chromatography / Diagnosis / Disease / Drug therapy / Female / Health aspects / Histocompatibility antigens / HLA histocompatibility antigens / HLA-DR Antigens - chemistry / HLA-DR Antigens - genetics / HLA-DR Antigens - immunology / HLA-DR Antigens - isolation & purification / HLA-DRB1 Chains / Humans / Identification and classification / Inflammation / Lavage / Lungs / Lymphocytes / Male / Mass spectrometry / Middle Aged / Molecular Sequence Data / NATURAL SCIENCES / NATURVETENSKAP / Peptides / Peptides - chemistry / Peptides - genetics / Peptides - metabolism / Protein Binding / Proteins / Sarcoidosis / Sarcoidosis, Pulmonary - genetics / Sarcoidosis, Pulmonary - immunology / Sarcoidosis, Pulmonary - pathology / Scientific imaging / Technical Advance