Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cellular proteins associated with immunodeficiency viruses were identified by determination of the amino acid sequence of the proteins and peptides present in sucrose density gradient-purified human immunodeficiency virus (HIV)-1, HIV-2, and simian immunodeficiency virus (SIV). beta 2 microglobulin (beta 2m) and the alpha and beta chains of human lymphocyte antigen (HLA) DR were present in virus preparations at one-fifth the concentration of Gag on a molar basis. Antisera to HLA DR, beta 2 m, as well as HLA class I precipitated intact viral particles, suggesting that these cellular proteins were physically associated with the surface of the virus. Antisera to class I, beta 2m, and HLA DR also inhibited infection of cultured cells by both HIV-1 and SIV. The specific, selective association of these cellular proteins in a physiologically relevant manner has major implications for our understanding of the infection process and the pathogenesis of immunodeficiency viruses and should be considered in the design of vaccines.
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PMID:Cellular proteins bound to immunodeficiency viruses: implications for pathogenesis and vaccines. 147 Sep 11

A HLA-A3.1-restricted CD8+ cytotoxic T-cell clone, E7.20, that lyses cells infected with human immunodeficiency virus type 1 was isolated from an infected individual. The epitope was localized to amino acids 768-778 (RLRDLLLIVTR, NL43 env sequence) of the cytoplasmic domain of gp41 by successive use of a panel of recombinant vaccinia viruses that express truncated env genes and synthetic peptides. The epitope is conserved on 7 (NL43, BRU, HXB2, BRVA, SC, JH3, and JFL) of 13 human immunodeficiency virus type 1 isolates from North America. Synthetic peptides of this region of strains RF and CDC4 are also recognized by E7.20 despite a nonconservative Thr----Val or Thr----Ala change at amino acid 777; however, an MN peptide, which has four amino acid substitutions, was not reactive. The epitope recognized by E7.20 has a predicted hydrophobic alpha-helical structure, with three contiguous Leu residues followed by Ile and Val at amino acids 772-776. Cytotoxicity was restricted by HLA-A3.1 using allogeneic target cells that shared HLA class I antigens with the donor and an HLA-A and -B negative human plasma cell line transfected with the HLA-A3.1 gene. The transfected cells were infectable by human immunodeficiency virus type 1 strains IIIB and MN but only the former virus sensitized them to killing by E7.20. The ability of E7.20 to specifically lyse a human lymphocyte line infected with a human immunodeficiency virus type 1 strain carrying the conserved epitope is consistent with an important role for cytotoxic T cells in controlling infection.
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PMID:Specific lysis of human immunodeficiency virus type 1-infected cells by a HLA-A3.1-restricted CD8+ cytotoxic T-lymphocyte clone that recognizes a conserved peptide sequence within the gp41 subunit of the envelope protein. 171 55

There are many examples of inherited immunodeficiencies characterized by normal differentiation of T and B lymphocytes but abnormal functions of these cells. Among them, combined immunodeficiency with defective expression in MHC class II genes was the first to be individualized. It is called MHC class deficient SCID by the WHO committee for the classification of immunodeficiency. It is an autosomal recessive disease with a severe evolution. Most of the 30 patients described died unless they were transplanted with HLA identical or HLA mismatched bone marrow. All HLA class II molecules (DR, DQ, and DP specificities) are absent on the cell surface in all tissues while HLA class I molecules are detectable. T and B cell abnormalities are characterized by defective in vivo and in vitro responses to antigens, although in vitro reactivity to mitogens is normal. These anomalies are considered as a direct consequence of the absence of HLA class II molecules on the surface of antigen-presenting cells incapable of sensitizing T cells. It was strongly suggested that MHC class II deficient SCID is due to a mutation that affects the regulation of the expression of all genes involved in the synthesis of MHC class II molecules.
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PMID:Combined immunodeficiency with defective expression in major histocompatibility complex class II genes. 193 8

The human leukocyte antigens (HLA) are implicated in the genetic susceptibility to a large number of diseases. Some of the diseases associated with HLA class II are related to specific amino acids or epitopes of the domain of the HLA class II molecule that is distal to the membrane. In man, selective immunoglobulin A deficiency is the most common immunodeficiency, frequently resulting in recurrent sino-pulmonary infections and gastro-intestinal disorders. Associations have been described with HLA class I, and to a lesser extent with different class II alleles, which might indicate that they share some common feature. Here we study 95 IgA-D patients and find positive associations with three DR-DQ haplotypes and a strong negative association with a fourth haplotype. Comparison of the sequences of the polymorphic amino-terminal domain of the DQ beta chain showed that the three 'susceptibility' haplotypes all had a neutral alanine or valine at position 57. The 'protective' allele had the negatively charged aspartic acid at this position (Asp57). Codon 57 of the HLA-DQ beta chain has been implicated in the susceptibility to insulin-dependent diabetes mellitus. Our data suggest that the same amino acid position could possibly also influence susceptibility and resistance to selective immunoglobulin A deficiency.
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PMID:Different amino acids at position 57 of the HLA-DQ beta chain associated with susceptibility and resistance to IgA deficiency. 197 29

We have examined the capacity of monoclonal antibodies (mAb) specific for HLA class I heavy chain to interfere with the human immunodeficiency virus (HIV) replicative cycle in human T cells. Among six anti-HLA class I heavy chain-specific mAb assayed, two mAb, RL4-24-6 and W6/32, were able to delay HIV1 and HIV2 cytopathic effect on MT4 cells, a human T cell leukemia virus type I (HTLVI) immortalized T cell line, mAb RL4-24-6, chosen for further studies, also inhibited HIV1 production by peripheral blood mononuclear cells (PBMC), and this inhibition was dose dependent. However, no effect was observed when mAb treatment was performed with either the CEM or Jurkat T cell lines. Our investigation of how RL4-24-6 interferes with the HIV replicative cycle revealed that: (a) incubation of PBMC with RL4-24-6 prior to HIV exposure did not change the susceptibility of these cells to HIV infection, (b) syncytia formation between CD4+ MT4 cells and HIV chronically infected PBMC was not affected by RL4-24-6 and (c) treatment of freshly infected PBMC with RL4-24-6, however, inhibited viral production. These data, together with those we previously reported using anti-beta 2-microglobulin (beta 2m) mAb, suggest that anti-HLA class I/beta 2m complex mAb can modify an early step of the HIV replicative cycle without affecting the viral entry.
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PMID:Anti-HLA antigen class I heavy chain monoclonal antibodies inhibit human immunodeficiency virus production by peripheral blood mononuclear cells. 201 88

It has been well established that psoriasis, psoriatic arthritis, and Reiter's syndrome can occur in patients with HIV infection. These arthocutaneous diseases tend to occur in temporal proximity to the development of AIDS and ARC, and their clinical manifestations are unusually severe. The appearance or exacerbation of psoriasis, arthritis, or Reiter's syndrome in a high-risk person should alert the clinician to possible underlying HIV infection. Treatment should be dictated by the severity of the skin and musculoskeletal disease as well as by the status of the immune system. Zidovudine appears to be effective in many diseases, especially psoriasis, and nonsteroidal antiinflammatory drugs are the mainstay for arthritis. Immunosuppressive agents such as methotrexate and azathioprine are contraindicated because they exacerbate immunodeficiency and promote infections. Epidemiologic studies suggest that the prevalence of these diseases, especially Reiter's syndrome, may be higher in HIV-positive populations than previously thought, especially in those patients with AIDS and ARC. Immunogenetic factors like HLA-B27 are important in the predisposition to Reiter's syndrome associated with HIV infection; however, it is not clear what role they play in HIV-associated psoriasis. Mechanisms underlying these observations remain unclear, although potential insights into the pathogeneses of psoriasis and Reiter's syndrome may be gained through future studies. Already it seems likely that CD4-positive helper T-cells, the target of HIV, are not necessary for the expression of psoriasis or Reiter's syndrome, and because of HLA class I associations, a role for CD8 positive cytotoxic T lymphocytes can be suspected. Infections, promoted by the profound immunodeficiency of AIDS, seem to be the most plausible explanations for the cutaneous and articular complications of HIV infection.
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PMID:Psoriasis and psoriatic arthritis associated with human immunodeficiency virus infection. 204 89

HLA Class I soluble antigen serum levels have been evaluated in 178 subjects who were positive for human immunodeficiency virus (HIV) and in 66 HIV-negative controls. The serum levels of HIV p24 antigen, interleukin 2 receptor (IL 2r), CD8 soluble antigen (CD 8ag), B2-microglobulin (B2-m), and neopterin (Npt), as well as the number of CD4+ and CD8+ T cells were also evaluated. Results show that mean HLA class I serum levels of HIV-positive subjects: (1) are significantly higher than controls (p less than 0.001); (2) increase with disease progression (67.7 RU/ml, 103.4 RU/ml, and 169.6 RU/ml for subjects belonging to groups II, II, and IV of the Centers for Disease Control [CDC] classification, respectively); (3) correlate with HIV p24 antigen, IL2r, and CD 8 soluble antigen levels. Present data show that elevated levels of HLA class I soluble antigens, correlating with disease stage, are found in sera of HIV-positive subjects. Circulating HLA class I molecules, interfering with some immune functions, might contribute to the pathogenesis of the immune deficiency of HIV-positive subjects.
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PMID:HLA class I soluble antigen serum levels in HIV-positive subjects--correlation with cellular and serological parameters. 211 84

By using target cells that expressed only the regulatory NEF protein of the human immunodeficiency virus (HIV), we were able to identify specific cytolytic T cells (CTL) from most of the seropositive patients tested. This NEF-specific cytolytic activity was mediated by CD8+ lymphocytes. In two different donors, we identified a unique peptide in the NEF protein that could be recognized in association with two different HLA class I molecules. The definition of such a peptide should prove useful in evaluating vaccine strategies.
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PMID:An antigenic peptide of the HIV-1 NEF protein recognized by cytotoxic T lymphocytes of seropositive individuals in association with different HLA-B molecules. 248 93

A variety of clinical syndromes, including AIDS and neurological disorders, may follow as a consequence of infection with the human immunodeficiency virus type 1 (HIV-1). It is not yet clear, however, to what extent the destruction of lymphocytes and neural cells associated with these conditions is caused by adverse immune responses to HIV-1 or how much is due to cytopathic effects of the virus itself. Here we document the existence of HLA-restricted, HIV-1-specific cytotoxic T lymphocytes in the cerebrospinal fluid of two AIDS patients manifesting neurologic disorders. These cytotoxic T lymphocytes showed dual specificity, recognizing target cells coated with purified HIV-1 envelope glycoprotein (gp 120) or inactivated HIV-1 in the context of HLA antigens. Cytotoxic T-cell clones derived from one of the AIDS patients revealed restriction specificities representing both HLA class I and HLA class II antigens. Considerable phenotypic heterogeneity was observed amongst these clones, some expressing conventional combinations of cytotoxic T-cell surface markers, and others displaying unusual phenotypes. The presence of HIV-specific cytotoxic T lymphocytes in AIDS patients, and in particular in their cerebrospinal fluid, suggests that these cytotoxic effectors may participate in the lymphoid cell and/or neurologic damage observed in such patients.
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PMID:Phenotypic heterogeneity of cerebrospinal fluid-derived HIV-specific and HLA-restricted cytotoxic T-cell clones. 284 92

The anti-HLA reactivity of sera from 210 heroin addicts was tested by the direct binding with 125I-labeled preparations of HLA class I and class II molecules purified from human B-cell lines of various HLA haplotypes. A high proportion (81.7%) of the sera tested possessed anti-HLA class I and II reactivity. The reactivity did not show any allospecificity and was apparently mediated by antibodies. The control included 100 healthy blood donors, 25 male homosexuals positive for anti-HIV (human immunodeficiency virus) antibodies, and 25 patients positive for HBsAg (hepatitis B surface antigen). Of these controls, only one of the healthy blood donors was positive for anti-HLA reactivity (P much less than 0.001). Among heroin addicts, the reactivity was independent of the presence of either HBsAg or anti-HIV antibodies in the serum.
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PMID:A high proportion of sera of heroin addicts possesses anti-HLA class I and class II reactivity. 333 95


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