Document Detail

Beryllium presentation to CD4+ T cells is dependent on a single amino acid residue of the MHC class II beta-chain.
MedLine Citation:
PMID:  16272364     Owner:  NLM     Status:  MEDLINE    
Chronic beryllium disease (CBD) is characterized by a CD4+ T cell alveolitis and granulomatous inflammation in the lung. Genetic susceptibility to this disease has been linked with HLA-DP alleles, particularly those possessing a glutamic acid at position 69 (Glu69) of the beta-chain. However, 15% of CBD patients do not possess a Glu69-containing HLA-DP allele, suggesting that other MHC class II alleles may be involved in disease susceptibility. In CBD patients without a Glu69-containing HLA-DP allele, an increased frequency of HLA-DR13 alleles has been described, and these alleles possess a glutamic acid at position 71 of the beta-chain (which corresponds to position 69 of HLA-DP). Thus, we hypothesized that beryllium presentation to CD4+ T cells was dependent on a glutamic acid residue at the identical position of both HLA-DP and -DR. The results show that HLA-DP Glu69- and HLA-DR Glu71-expressing molecules are capable of inducing beryllium-specific proliferation and IFN-gamma expression by lung CD4+ T cells. Using fibroblasts expressing mutated HLA-DP2 and -DR13 molecules, beryllium recognition was dependent on the glutamic acid at position 69 of HLA-DP and 71 of HLA-DR, suggesting a critical role for this amino acid in beryllium presentation to Ag-specific CD4+ T cells. Thus, these results demonstrate that a single amino acid residue of the MHC class II beta-chain dictates beryllium presentation and potentially, disease susceptibility.
Jerome R Bill; Douglas G Mack; Michael T Falta; Lisa A Maier; Andrew K Sullivan; Fenneke G Joslin; Allison K Martin; Brian M Freed; Brian L Kotzin; Andrew P Fontenot
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  175     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  2005 Nov 
Date Detail:
Created Date:  2005-11-07     Completed Date:  2006-01-03     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7029-37     Citation Subset:  AIM; IM    
Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80206, USA.
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MeSH Terms
Amino Acid Sequence
Antigen Presentation*
Base Sequence
Berylliosis / etiology,  genetics*,  immunology*
Beryllium / immunology*,  toxicity
CD4-Positive T-Lymphocytes / immunology*
DNA, Complementary / genetics
HLA-DP Antigens / genetics*
HLA-DR Antigens / genetics*
Interferon-gamma / biosynthesis
Mutagenesis, Site-Directed
Grant Support
Reg. No./Substance:
0/DNA, Complementary; 0/HLA-DP Antigens; 0/HLA-DR Antigens; 7440-41-7/Beryllium; 82115-62-6/Interferon-gamma

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