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. 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.
Fontenot
A P
AP
Departments of Medicine and Immunology, University of Colorado Health Sciences Center, Denver, CO 80262, USA. andrew.fontenot@uchsc.edu
Torres
M
M
Marshall
W H
WH
Newman
L S
LS
Kotzin
B L
BL
D000483:Alleles; D017951:Antigen Presentation / Q000276:immunology*; D001607:Berylliosis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D001608:Beryllium / Q000009:adverse effects / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D002908:Chronic Disease; D004198:Disease Susceptibility; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006682:HLA-DP Antigens / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D059868:HLA-DP beta-Chains; D006683:HLA-DQ Antigens / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D059811:HLA-DRB1 Chains; D006801:Humans; D008168:Lung / Q000166:cytology
D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C020711:beryllium sulfate; D001608:Beryllium