| Beryllium presentation to CD4+ T cells is dependent on a single amino acid residue of the MHC class II beta-chain. | |
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MedLine Citation:
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PMID: 16272364 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 175 ISSN: 0022-1767 ISO Abbreviation: J. Immunol. Publication Date: 2005 Nov |
Date Detail:
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Created Date: 2005-11-07 Completed Date: 2006-01-03 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 7029-37 Citation Subset: AIM; IM |
Affiliation:
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Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80206, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alleles 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* Humans Interferon-gamma / biosynthesis Mutagenesis, Site-Directed |
| Grant Support | |
ID/Acronym/Agency:
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ES011810/ES/NIEHS NIH HHS; ES06358/ES/NIEHS NIH HHS; HL62410/HL/NHLBI NIH HHS; M01-RR00051/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/DNA, Complementary; 0/HLA-DP Antigens; 0/HLA-DR Antigens; 7440-41-7/Beryllium; 82115-62-6/Interferon-gamma |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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