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

J Clin Invest. 2007 Nov;117(11):3576-82. doi: 10.1172/JCI32401.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amino Acid Sequence
  • Bronchoalveolar Lavage Fluid / cytology*
  • Female
  • HLA-DR Antigens / chemistry
  • HLA-DR Antigens / genetics
  • HLA-DR Antigens / immunology*
  • HLA-DR Antigens / isolation & purification
  • HLA-DRB1 Chains
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Peptides / chemistry
  • Peptides / genetics
  • Peptides / metabolism*
  • Protein Binding
  • Sarcoidosis, Pulmonary / genetics
  • Sarcoidosis, Pulmonary / immunology*
  • Sarcoidosis, Pulmonary / pathology


  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • HLA-DRB1*03:01 antigen
  • Peptides