Role of high-affinity HLA-DP specific CLIP-derived peptides in beryllium binding to the HLA-DPGlu69 berylliosis-associated molecules and presentation to beryllium-sensitized T cells

Immunology. 2009 Sep;128(1 Suppl):e462-70. doi: 10.1111/j.1365-2567.2008.03000.x. Epub 2008 Dec 23.


Berylliosis is driven by the accumulation in the lung of beryllium-specific T helper type 1 (Th1) cells recognizing beryllium as antigen when presented principally by human leucocyte antigen DP molecules carrying a glutamate at position beta69 (HLA-DPGlu69). This study was designed to clarify the precise role of peptides in beryllium binding to the HLA-DP groove's pocket 4 and to identify peptides with higher affinity for pocket 4 that might prevent beryllium presentation and T-cell stimulation. Beryllium/HLA-DP interactions were analysed by the ability of beryllium to compete with CLIP and CLIP-derived peptides to HLA-DPGlu69 soluble molecule. The CLIP-derived low-affinity peptide CLIP-AA, could not outcompete beryllium; while the CLIP-derived high-affinity peptides CLIP-YY, CLIP-QY and CLIP-RF were only marginally influenced by the presence of beryllium in the competition assay. The effect of these CLIP-derived high-affinity peptides on beryllium presentation was determined by measuring interferon-gamma (IFN-gamma) release upon beryllium stimulation of peripheral blood mononuclear cells obtained from beryllium-hypersensitive subjects. CLIP-YY did inhibit beryllium presentation and T-cell activation, while CLIP-QY and CLIP-RF markedly enhanced the IFN-gamma response to beryllium. Anti-HLA-DP monoclonal antibody blocked the beryllium-induced IFN-gamma release in the presence of CLIP-QY (88%) and CLIP-RF (76%). A similar effect was observed for CLIP-YY capability to block IFN-gamma release by beryllium stimulation in the presence of CLIP-QY (79%) and CLIP-RF (76%). Overall, these data support the proposal that HLA-DP high-affinity peptides might be used as a model for specific berylliosis therapy.

Publication types

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

MeSH terms

  • Adult
  • Antigens, Differentiation, B-Lymphocyte / immunology*
  • Antigens, Differentiation, B-Lymphocyte / metabolism
  • Berylliosis / immunology*
  • Berylliosis / metabolism
  • Beryllium / immunology*
  • Beryllium / metabolism
  • Female
  • HLA-DP Antigens / chemistry
  • HLA-DP Antigens / immunology*
  • HLA-DP Antigens / metabolism
  • Histocompatibility Antigens Class II / immunology*
  • Histocompatibility Antigens Class II / metabolism
  • Humans
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism


  • Antigens, Differentiation, B-Lymphocyte
  • HLA-DP Antigens
  • Histocompatibility Antigens Class II
  • invariant chain
  • Interferon-gamma
  • Beryllium