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Role of Human Leukocyte Antigen-DP in the Presentation of Beryllium to T Cells in Chronic Beryllium Disease* FREE TO VIEW

Andrew P. Fontenot, MD; Michaelann Vollmer; Lee S. Newman, MD, FCCP; Brian L. Kotzin, MD
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*From the University of Colorado Health Sciences Center, Denver, CO.

Correspondence to: Andrew P. Fontenot, MD, Assistant Professor of Medicine, Division of Allergy and Clinical Immunology, University of Colorado Health Sciences Center, 4200 East Ninth Ave, Denver, CO 80262

Chest. 2001;120(1_suppl):S58. doi:10.1378/chest.120.1_suppl.S58
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Chronic beryllium disease (CBD) is caused by exposure to beryllium in the workplace and is characterized by CD4+ T-cell–mediated inflammation in the lung. This disease continues to be a major public health problem worldwide with approximately 800,000 individuals with current or past exposure. Susceptibility to CBD has been associated with particular human leukocyte antigen (HLA)-DP alleles, especially DPB1*0201. We developed beryllium-specific CD4+ T-cell lines from the lungs of four patients with CBD. These lines vigorously responded to beryllium sulfate (BeSO4) and failed to proliferate to other similar metals, such as Al2(SO4)3. Antibody-blocking experiments showed complete or near complete inhibition of proliferation with an anti-DP monoclonal antibody. To further characterize the restriction requirements for presentation, multiple antigen-presenting cells expressing different HLA-DP alleles were tested. The results indicated that only certain HLA-DP alleles allowed for presentation. For example, the CD4+ T-cell line from CBD patient 2 (DPB1*0201/0401) only responded to BeSO4 when presented by DPB1*0201 and not DPB1*0401. The lines from CBD patients 3 and 4 vigorously responded to BeSO4 when presented by either of their respective DP alleles (DPB1*0402 and *1001 or DPB1*0201 and *1701). These lines also responded to BeSO4 in the presence of DPB1*0201 but not DPB1*0401. Based on amino-acid residues shared by these HLA-DP alleles, the results pointed to residues in the α-helices of the binding groove being required for beryllium presentation. These results provide important insight into the pathogenesis of this disease and provide a clear explanation for why certain HLA-DP alleles predispose to disease.

Abbreviations: CBD = chronic beryllium disease; HLA = human leukocyte antigen




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