Fontenot A P, Torres M, Marshall W H, Newman L S, Kotzin B L
Departments of Medicine and Immunology, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
Proc Natl Acad Sci U S A. 2000 Nov 7;97(23):12717-22. doi: 10.1073/pnas.220430797.
Chronic beryllium disease results from beryllium exposure in the workplace and is characterized by CD4(+) T cell-mediated inflammation in the lung. Susceptibility to this disease is associated with particular HLA-DP alleles. We isolated beryllium-specific T cell lines from the lungs of affected patients. These CD4(+) T cell lines specifically responded to beryllium in culture in the presence of antigen-presenting cells that expressed class II MHC molecules HLA-DR, -DQ, and -DP. The response to beryllium was nearly completely and selectively blocked by mAb to HLA-DP. Additional studies showed that only certain HLA-DP alleles allowed presentation of beryllium. Overall, the DP alleles that presented beryllium to disease-specific T cell lines match those implicated in disease susceptibility, providing a mechanism for this association. Based on amino acid residues shared by these restricting and susceptibility DP alleles, our results provide insight into the residues of the DP beta-chain required for beryllium presentation.
慢性铍病是由工作场所接触铍引起的，其特征是肺部CD4(+) T细胞介导的炎症。对这种疾病的易感性与特定的HLA-DP等位基因有关。我们从受影响患者的肺部分离出铍特异性T细胞系。在表达II类MHC分子HLA-DR、-DQ和-DP的抗原呈递细胞存在的情况下，这些CD4(+) T细胞系在培养中对铍有特异性反应。对铍的反应几乎完全且选择性地被抗HLA-DP单克隆抗体阻断。进一步的研究表明，只有某些HLA-DP等位基因能够呈递铍。总体而言，将铍呈递给疾病特异性T细胞系的DP等位基因与那些与疾病易感性相关的等位基因相匹配，为这种关联提供了一种机制。基于这些限制性和易感性DP等位基因共有的氨基酸残基，我们的结果为铍呈递所需的DPβ链残基提供了见解。
