Search results for "major histocompatibility complex"
showing 10 items of 263 documents
Characterization of non-expressed C4 genes in a case of complete C4 deficiency: identification of a novel point mutation leading to a premature stop …
1998
The genetic basis of complete C4 deficiency in a patient with SLE was investigated. Previous studies have demonstrated that this patient has two different major histocompatibility complex (MHC) haplotypes that each contain a major deletion and a non-expressed C4 gene. In the present study, non-expression of the C4 genes was explained by the finding of two distinct C4 gene mutations. A previously described two base pair insertion in exon 29 of the C4 gene was detected in the paternal MHC haplotype [HLA-A2, B40, SC00, DR6]. The maternal haplotype [HLA-A30, B18, F1C00, DR3] carried a C4 gene with a one base pair deletion in exon 20 generating a premature stop codon. This mutation was neither f…
HLA-B8,DR3 haplotype affects lymphocyte blood levels
1997
The number of lymphocytes in the blood is constant, pointing to an effective control of circulating lymphocyte values. The mechanisms of this regulation are uncertain, although it is likely that the number of blood lymphocytes is conditioned by hormones, homing factors and cytokines whose production is at least partly restrained by genetic factors. Particularly genetic factors linked to major histocompatibility complex (MHC) appear to be involved. In human beings a decreased number of blood lymphocytes has been described in healthy subjects carrying the Human Leucocyte Antigens (HLA) haplotype HLA-B8,DR3. In the present study, to inquire into the mechanisms of this lymphocyte decreased numb…
An Intergenic rs9275596 Polymorphism on Chr. 6p21 Is Associated with Multiple Sclerosis in Latvians
2020
Background and objectives: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, leading to demyelination of neurons and potentially debilitating physical and mental symptoms. The disease is more prevalent in women than in men. The major histocompatibility complex (MHC) region has been identified as a major genetic determinant for autoimmune diseases, and its role in some neurological disorders including MS was evaluated. An intergenic single-nucleotide polymorphism (SNP), rs9275596, located between the HLA-DQB1 and HLA-DQA2 genes, is in significant association with various autoimmune diseases according to genome-wide association studies (GWASs). A cumulat…
Immune-mediated necrotizing myopathy is characterized by a specific Th1-M1 polarized immune profile.
2012
Immune-mediated necrotizing myopathy (IMNM) is considered one of the idiopathic inflammatory myopathies, comprising dermatomyositis, polymyositis, and inclusion body myositis. The heterogeneous group of necrotizing myopathies shows a varying amount of necrotic muscle fibers, myophagocytosis, and a sparse inflammatory infiltrate. The underlying immune response in necrotizing myopathy has not yet been addressed in detail. Affected muscle tissue, obtained from 16 patients with IMNM, was analyzed compared with eight non-IMNM (nIMNM) tissues. Inflammatory cells were characterized by IHC, and immune mediators were assessed by quantitative real-time PCR. We demonstrate that immune- and non–immune-…
HLA-B27-derived peptides as autoantigens for T lymphocytes in ankylosing spondylitis
1997
Objective.To study whether peptides derived from the HLA-B27 molecule sequence can stimulate peripheral blood T lymphocytes (PBL) from patients with HLA-B27-associated spondylarthropathies. Methods.PBL from 55 HLA-B27+ patients with ankylosing spondylitis (AS), 28 HLA-B27+ patients with other spondylarthropathies, 7 rheumatoid arthritis patients, and 30 HLA-B27+ and 22 HLA-B27- healthy controls were tested in lymphocyte proliferation assays with 4 synthetic peptides derived from the HLA-B*2705 molecule. Results. A 13-mer peptide (B27PA) induced significant proliferative responses in 17 of the 55 AS patients (stimulation index [SI] 2.5–17.5), as well as in 3 of the HLA-B27+ healthy controls …
Major histocompatibility complex and sporadic Alzheimer's disease: a critical reappraisal
2003
Epidemiological data suggest that some genetic determinants of Alzheimer's disease (AD) might reside in those polymorphisms for the immune system genes that regulate immune inflammatory responses, such as the major histocompatibility complex (MHC). Therefore, MHC polymorphisms have been the focus of a large number of AD association studies. Class Ia, Ib (hemochromatosis gene (HFE)), class II and class III (complement, tumour necrosis factor and heat shock proteins) alleles have been studied. Nearly every positive result has been followed by several studies that have failed to replicate it or that have contradicted it. Several factors, including methodological biases, might explain these dis…
Activation by mitogens and superantigens of axolotl lymphocytes: functional characterization and ontogenic study.
1996
Urodele amphibians have weak and slow immune responses compared to mammals and anuran amphibians. Using new culture conditions, we tested the ability of lymphocytes of a well-studied salamander, the Mexican axolotl (Ambystoma mexicanum) to proliferate in vitro with diverse mitogenic agents. We demonstrated that the axolotl has a population of B lymphocytes that proliferate specifically and with a high stimulation index to the lipopolysaccharide (LPS) known as a B-cell mitogen in mammals. This proliferative capacity is observed without significant changes throughout ontogenesis. In the presence of LPS, axolotl B lymphocytes are able to synthesize and secrete both isotopes of immunoglobulin d…
Early activation of γδ T lymphocytes in the elderly
2001
T cell function is altered in vivo and in vitro in elderly compared with young subjects, and this alteration is believed to contribute to morbidity and mortality in man due to the greater incidence of infection, as well as autoimmunity and cancer in elderly. The majority of T cells express TCRalphabeta whereas TCRgammadelta is expressed on a minority of T cells. Moreover, it is known that gammadelta T lymphocytes display major histocompatibility complex (MHC)- unrestricted cytotoxicity that is reminiscent of natural killer (NK) activity. In view of earlier findings on both T cells and NK cells in the elderly, we hypothesised a different behaviour of gammadelta T lymphocytes from old subject…
IL-21 Regulates the Differentiation of a Human γδ T Cell Subset Equipped with B Cell Helper Activity
2012
Vγ9Vδ2 T lymphocytes recognize nonpeptidic antigens without presentation by MHC molecules and display pleiotropic features. Here we report that coculture of Vγ9Vδ2 cells with phosphoantigen and IL-21 leads to selective expression of the transcription repressor Bcl-6 and polarization toward a lymphocyte subset displaying features of follicular B-helper T (T(FH)) cells. T(FH) like Vγ9Vδ2 cells have a predominant central memory (CD27(+)CD45RA(-)) phenotype and express ICOS, CD40L and CXCR5. Upon antigen activation, they secrete IL-4, IL-10 and CXCL13, and provide B-cell help for antibody production in vitro. Our findings delineate a subset of human Vγ9Vδ2 lymphocytes, which, upon interaction w…
Cellular and humoral immune responses against cancer: implications for cancer vaccines.
1991
The key issue in tumor immunology is to identify antigens as target structures for a cancer-selective immunological attack in the tumor-bearing host, resulting in tumor rejection. There is a growing detailed understanding of structural and regulatory gene alterations giving rise to candidate rejection antigens and peptides in tumor cells. As well as reviewing the development of new adjuvant and recombinant vector systems, new approaches are suggested for the construction of cancer vaccines.