Beryllium presentation to CD4(+) T cells underlies disease-susceptibility HLA-DP alleles in chronic beryllium disease

Chronic beryllium disease results from beryllium exposure in the workplace and is characterized by CD4(+) T cell-mediated inflammation in the lung. Su sceptibility to this disease is associated with particular HLA-DP alleles. We isolated beryllium-specific T cell lines from the lungs of affected pati ents. These CD4(+) T cell lines specifically responded to beryllium in cult ure in the presence of antigen-presenting cells that expressed class II MHC molecules HLA-DR, -DQ, and -DP. The response to beryllium was nearly compl etely and selectively blocked by mAb to HLA-DP. Additional studies showed t hat only certain HLA-DP alleles allowed presentation of beryllium. Overall. the DP alleles that presented beryllium to disease-specific T cell lines m atch 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 residue s of the DP beta -chain required for beryllium presentation.