دورية أكاديمية
Beryllium presentation to CD4+ T cells is dependent on a single amino acid residue of the MHC class II beta-chain.
العنوان: | 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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المؤلفون: | Bill JR; Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80206, USA., Mack DG, Falta MT, Maier LA, Sullivan AK, Joslin FG, Martin AK, Freed BM, Kotzin BL, Fontenot AP |
المصدر: | Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2005 Nov 15; Vol. 175 (10), pp. 7029-37. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
اللغة: | English |
بيانات الدورية: | Publisher: American Association of Immunologists Country of Publication: United States NLM ID: 2985117R Publication Model: Print Cited Medium: Print ISSN: 0022-1767 (Print) Linking ISSN: 00221767 NLM ISO Abbreviation: J Immunol Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Bethesda, MD : American Association of Immunologists Original Publication: Baltimore : Williams & Wilkins, c1950- |
مواضيع طبية MeSH: | Antigen Presentation*, Berylliosis/*genetics , Berylliosis/*immunology , Beryllium/*immunology , CD4-Positive T-Lymphocytes/*immunology , HLA-DP Antigens/*genetics , HLA-DR Antigens/*genetics, Alleles ; Amino Acid Sequence ; Base Sequence ; Berylliosis/etiology ; Beryllium/toxicity ; DNA, Complementary/genetics ; Humans ; In Vitro Techniques ; Interferon-gamma/biosynthesis ; Mutagenesis, Site-Directed |
مستخلص: | 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. |
معلومات مُعتمدة: | ES06358 United States ES NIEHS NIH HHS; ES011810 United States ES NIEHS NIH HHS; HL62410 United States HL NHLBI NIH HHS; R01 HL062410 United States HL NHLBI NIH HHS; M01-RR00051 United States RR NCRR NIH HHS |
المشرفين على المادة: | 0 (DNA, Complementary) 0 (HLA-DP Antigens) 0 (HLA-DR Antigens) 82115-62-6 (Interferon-gamma) OW5102UV6N (Beryllium) |
تواريخ الأحداث: | Date Created: 20051108 Date Completed: 20060103 Latest Revision: 20190516 |
رمز التحديث: | 20240829 |
DOI: | 10.4049/jimmunol.175.10.7029 |
PMID: | 16272364 |
قاعدة البيانات: | MEDLINE |
تدمد: | 0022-1767 |
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DOI: | 10.4049/jimmunol.175.10.7029 |