Beryllium presentation to CD4+ T cells is dependent on a single amino acid residue of the MHC class II beta-chain

J Immunol. 2005 Nov 15;175(10):7029-37. doi: 10.4049/jimmunol.175.10.7029.


Chronic beryllium disease (CBD) is characterized by a CD4+ T cell alveolitis and granulomatous inflammation in the lung. Genetic susceptibility to this disease has been linked with HLA-DP alleles, particularly those possessing a glutamic acid at position 69 (Glu69) of the beta-chain. However, 15% of CBD patients do not possess a Glu69-containing HLA-DP allele, suggesting that other MHC class II alleles may be involved in disease susceptibility. In CBD patients without a Glu69-containing HLA-DP allele, an increased frequency of HLA-DR13 alleles has been described, and these alleles possess a glutamic acid at position 71 of the beta-chain (which corresponds to position 69 of HLA-DP). Thus, we hypothesized that beryllium presentation to CD4+ T cells was dependent on a glutamic acid residue at the identical position of both HLA-DP and -DR. The results show that HLA-DP Glu69- and HLA-DR Glu71-expressing molecules are capable of inducing beryllium-specific proliferation and IFN-gamma expression by lung CD4+ T cells. Using fibroblasts expressing mutated HLA-DP2 and -DR13 molecules, beryllium recognition was dependent on the glutamic acid at position 69 of HLA-DP and 71 of HLA-DR, suggesting a critical role for this amino acid in beryllium presentation to Ag-specific CD4+ T cells. Thus, these results demonstrate that a single amino acid residue of the MHC class II beta-chain dictates beryllium presentation and potentially, disease susceptibility.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Antigen Presentation*
  • Base Sequence
  • Berylliosis / etiology
  • Berylliosis / genetics*
  • Berylliosis / immunology*
  • Beryllium / immunology*
  • Beryllium / toxicity
  • CD4-Positive T-Lymphocytes / immunology*
  • DNA, Complementary / genetics
  • HLA-DP Antigens / genetics*
  • HLA-DR Antigens / genetics*
  • Humans
  • In Vitro Techniques
  • Interferon-gamma / biosynthesis
  • Mutagenesis, Site-Directed


  • DNA, Complementary
  • HLA-DP Antigens
  • HLA-DR Antigens
  • Interferon-gamma
  • Beryllium