Beryllium binding to HLA-DP molecule carrying the marker of susceptibility to berylliosis glutamate beta 69

Hum Immunol. 2001 Jul;62(7):686-93. doi: 10.1016/s0198-8859(01)00261-0.


Berylliosis is a chronic granulomatous disorder caused by inhalation of Be dusts that is driven by the accumulation of Be-specific CD4+ Th1-cells at disease sites. Susceptibility to berylliosis has been associated with the supratypic variant of HLA-DP gene coding for glutamate at position beta69 (HLA-DPbetaGlu69). The aim of this study was to test the hypothesis that the HLA-DPbetaGlu69 residue plays a role in the interaction with Be. To this end, soluble HLA-DP2 molecule (carrying betaGlu69) and its mutated form carrying lysine at position beta69 (HLA-DP2Lys69) were produced in Drosophila melanogaster and then used in a Be binding assays. BeSO4 (1-1000 microM) was used to compete for the binding of the biotinilated invariant chain-derived peptide CLIP (50 microM). BeSO4 was capable of compete out biotin-CLIP binding from the HLA-DP2 (IC50%: 4.5 microM of BeSO4 at pH 5.0 and 5.5 microM of BeSO4 at pH 7.5), but not from the HLA-DP2Lys69 molecule (IC50%: 480 microM of BeSO4 at pH 5.0 and 220 microM of BeSO4 at pH 7.5). Moreover, the binding of NFLD.M60, a MoAb recognizing an epitope in the HLA-DP peptide binding region, to the HLA-DP2, but not to the HLA-DP2Lys69 soluble molecules was inhibited BeSO4. NFLD.M60 binding to HLA-DP2, but not to HLA-DP2Lys69 stably transfected murine cells was also inhibited by Be both at pH 5.0 and at pH 7.5. The data indicate a direct interaction of Be with the HLA-DPGlu69 molecule, in the absence of antigen processing.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution / genetics
  • Amino Acid Substitution / immunology
  • Animals
  • Berylliosis / genetics
  • Berylliosis / immunology*
  • Beryllium / immunology*
  • Beryllium / metabolism*
  • Biomarkers
  • Cell Line
  • Drosophila melanogaster / genetics
  • Genetic Predisposition to Disease*
  • Genetic Vectors
  • Glutamic Acid / genetics*
  • Glutamic Acid / metabolism
  • HLA-DP Antigens / biosynthesis
  • HLA-DP Antigens / genetics
  • HLA-DP Antigens / isolation & purification
  • HLA-DP Antigens / metabolism*
  • Humans
  • Lysine / genetics
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Protein Binding / immunology
  • Solubility


  • Biomarkers
  • HLA-DP Antigens
  • Glutamic Acid
  • Lysine
  • Beryllium