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

J Wahlström, J Dengjel, B Persson… - The Journal of …, 2007 - Am Soc Clin Investig
J Wahlström, J Dengjel, B Persson, H Duyar, HG Rammensee, S Stevanović, A Eklund…
The Journal of clinical investigation, 2007Am Soc Clin Investig
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 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.
The Journal of Clinical Investigation