Identification of multiple public TCR repertoires in chronic beryllium disease

J Immunol. 2014 May 15;192(10):4571-80. doi: 10.4049/jimmunol.1400007. Epub 2014 Apr 9.


Chronic beryllium disease (CBD) is a granulomatous lung disease characterized by the accumulation of beryllium (Be)-specific CD4(+) T cells in bronchoalveolar lavage. These expanded CD4(+) T cells are composed of oligoclonal T cell subsets, suggesting their recruitment to the lung in response to conventional Ag. In the current study, we noted that all bronchoalveolar lavage-derived T cell lines from HLA-DP2-expressing CBD patients contained an expansion of Be-responsive Vβ5.1(+) CD4(+) T cells. Using Be-loaded HLA-DP2-peptide tetramers, the majority of tetramer-binding T cells also expressed Vβ5.1 with a highly conserved CDR3β motif. Interestingly, Be-specific, Vβ5.1-expressing CD4(+) T cells displayed differential HLA-DP2-peptide tetramer staining intensity, and sequence analysis of the distinct tetramer-binding subsets showed that the two populations differed by a single conserved amino acid in the CDR3β motif. TCR Vα-chain analysis of purified Vβ5.1(+) CD4(+) T cells based on differential tetramer-binding intensity showed differing TCR Vα-chain pairing requirements, with the high-affinity population having promiscuous Vα-chain pairing and the low-affinity subset requiring restricted Vα-chain usage. Importantly, disease severity, as measured by loss of lung function, was inversely correlated with the frequency of tetramer-binding CD4(+) T cells in the lung. Our findings suggest the presence of a dominant Be-specific, Vβ5.1-expressing public T cell repertoire in the lungs of HLA-DP2-expressing CBD patients using promiscuous Vα-chain pairing to recognize an identical HLA-DP2-peptide/Be complex. Importantly, the inverse relationship between expansion of CD4(+) T cells expressing these public TCRs and disease severity suggests a pathogenic role for these T cells in CBD.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Berylliosis / genetics
  • Berylliosis / immunology*
  • Berylliosis / metabolism
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / pathology
  • Chronic Disease
  • Female
  • Gene Expression Regulation / immunology*
  • HLA-DP beta-Chains / biosynthesis
  • HLA-DP beta-Chains / genetics
  • HLA-DP beta-Chains / immunology
  • Humans
  • Lung / immunology*
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Molecular Sequence Data
  • Receptors, Antigen, T-Cell, alpha-beta / biosynthesis
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*


  • HLA-DP beta-Chains
  • HLA-DPw2 antigen
  • Receptors, Antigen, T-Cell, alpha-beta

Associated data

  • GENBANK/KJ026955
  • GENBANK/KJ026956
  • GENBANK/KJ026957
  • GENBANK/KJ026958
  • GENBANK/KJ026959
  • GENBANK/KJ026960