Aspartic acid homozygosity at codon 57 of HLA-DQ beta is associated with susceptibility to pulmonary tuberculosis in Cambodia
| Autor: | Anne E. Goldfeld, Julio C. Delgado, Sok Thim, Andres Baena |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Adult
CD4-Positive T-Lymphocytes Male Models Molecular Tuberculosis Adolescent Protein Conformation Immunology Molecular Sequence Data Human leukocyte antigen Cell Line Mycobacterium tuberculosis Cohort Studies Interferon-gamma Immune system Bacterial Proteins Polymorphism (computer science) Transduction Genetic HLA-DQ Antigens HLA-DQ Null cell medicine Immunology and Allergy HLA-DQ beta-Chains Humans Amino Acid Sequence Allele Codon Tuberculosis Pulmonary Antigen Presentation Antigens Bacterial Aspartic Acid Binding Sites Polymorphism Genetic biology Base Sequence Homozygote DNA Middle Aged biology.organism_classification medicine.disease Virology Case-Control Studies Female Cambodia |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 176(2) |
| ISSN: | 0022-1767 |
| Popis: | After infection with Mycobacterium tuberculosis, clinical disease usually remains latent, contained by the host immune response. Although polymorphisms of HLA loci have been hypothesized to play a major role in the breakdown of latency, a functional link has not been established. Molecular-based HLA-typing methods were used to test the association of sets of HLA alleles encoding an aspartic acid at codon 57 of the HLA-DQ β-chain (HLA-DQ β57-Asp) with susceptibility to tuberculosis in a cohort of 436 pulmonary tuberculosis patients and 107 healthy controls from Cambodia. HLA class II null cells were transduced with HLA-DQ β57-Asp or HLA-DQ β57-Ala and evaluated for their ability to bind peptides from two immunogenic M. tuberculosis specific proteins, ESAT-6 and CFP-10. In this study, we report a highly significant association between progressive pulmonary tuberculosis and homozygosity for HLA-DQ β57-Asp alleles. The presence of HLA-DQ β57-Asp resulted in a significantly reduced ability to bind a peptide from the central region of the ESAT-6 protein. Furthermore, when this peptide was presented by an HLA-DQ β57-Asp allele, Ag-specific IFN-γ production from CD4+ T cells from tuberculosis patients was significantly less than when this peptide was presented by an HLA-DQ-β allele encoding an alanine at codon 57. Multiple genetic loci and ethnic-specific factors are likely involved in the human immune response to tuberculosis. The data presented here provide a functional explanation for a highly significant association between an HLA polymorphism and tuberculosis in a highly characterized group of patients with susceptibility to progressive tuberculosis infection in Cambodia. |
| Databáze: | OpenAIRE |
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