Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

We recently found (C. Devaux, J. Boucraut, G. Poirier, P. Corbeau, F. Rey, M. Benkirane, B. Perarneau, F. Kourilsky, and J.C. Chermann, submitted for publication) a latency in the human immunodeficiency virus (HIV) type 1 cytopathic effect in the human T-cell lymphotropic virus type I immortalized T-cell line MT4 that was mediated by anti-beta 2 microglobulin (beta 2m) monoclonal antibodies (MAb). Here we describe a delay in viral particle production in peripheral blood mononuclear cells (PBMC) that was mediated by three (B1-1G6, B2-62-2, and HC11-151-1) of four anti-beta 2m MAb tested, the nonefficient MAb (C21-48A) being specific for an epitope on beta 2m that was masked by association with the human leukocyte antigen class I heavy chain. Experiments were designed to determine the mechanism of interference. PBMC incubated with anti-beta 2m MAb before viral exposure were not protected from HIV infection. In addition, anti-beta 2m MAb were not efficient in preventing syncytium formation between HIV-infected PBMC and CD4-positive MT4 cells. In contrast, anti-beta 2m MAb treatment of freshly infected PBMC significantly delayed HIV production in these cells. The window of cell sensitivity to anti-beta 2m MAb treatment took place during a very early post-HIV-binding stage. The possible mechanism of anti-beta 2m MAb action is discussed.
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PMID:An early postinfection signal mediated by monoclonal anti-beta 2 microglobulin antibody is responsible for delayed production of human immunodeficiency virus type 1 in peripheral blood mononuclear cells. 169 Aug 21

Virus-specific cytotoxic T lymphocytes (CTL) may be an important host defense mechanism in the control of virus replication in persons infected with human immunodeficiency virus type 1 (HIV-1). Cytotoxic T-cell lines generated by nonspecific stimulation with anti-CD3 monoclonal antibodies and interleukin 2 were used to identify regions within the HIV-1 Gag protein that are the most frequently recognized. Using autologous Epstein-Barr virus-transformed target cells infected with recombinant vaccinia viruses encoding p18gag, p24gag, and p55gag proteins of HIV-1/Lai or selected truncations of p24gag, we show that within a group of 29 infected subjects, the p24gag protein is the target of Gag-specific CTL in most donors. Using autologous Epstein-Barr virus-transformed target cells coated with different synthetic peptides spanning the Gag amino acid sequence, we found clusters of partially overlapping peptides in three conserved regions of the p24 protein (amino acids [aa] 169 to 192, aa 219 to 304, and aa 335 to 372) that are frequently recognized by CTL and presented by a variety of human leukocyte antigen class I molecules. Since there are experiments both in vitro and in vivo showing the role of CTL in the control of virus replication in HIV and simian immunodeficiency virus infections, these results may be particularly important for vaccine development.
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PMID:Gag-specific cytotoxic T lymphocytes from human immunodeficiency virus type 1-infected individuals: Gag epitopes are clustered in three regions of the p24gag protein. 767 3

In addition to CD4, the primary receptor to which the human immunodeficiency virus type 1 (HIV-1) binds, mononuclear phagocytes (monocytes) express three classes of Fc receptors for immunoglobulin G (Fc gamma R). We have previously shown that infection of monocytes by HIV-1 is inhibited when bispecific antibodies (BsAbs) are used to target the virus to either the type I, type II, or type III Fc gamma R on these cells. Infection of monocytes was not inhibited when HIV-1 was targeted to either human leukocyte antigen class I or CD33. We have extended these studies to examine the ability of BsAbs plus polymorphonuclear leukocytes (neutrophils, PMNs) and monocytes to reduce infectivity of HIV-1 to cells from the human T cell lymphoma line, H9. The production of HIV-1 following interaction of virus with BsAb and phagocytes was determined in an indicator cell assay by mixing BsAb, HIV-1, and phagocytes with uninfected H9 cells. Productive infection of H9 cells was quantitated on subsequent days by measuring p24 gag antigen levels in supernatants by enzyme-linked immunosorbent assay. Our findings show that the addition of interferon-gamma-activated PMNs or monocytes to cultures of HIV-1 plus H9 cells in the absence of BsAb results in a marked reduction in p24 levels equivalent to 85 to 90% of control levels. With the combination of BsAb (anti-Fc gamma RI x anti-gp120) plus IFN-gamma-activated phagocytes, levels of p24 in H9 cultures were below those at culture initiation. These findings demonstrate that IFN-gamma-activated phagocytes can affect the natural course of HIV-1 infection of T cells, a finding of potential clinical importance.
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PMID:Targeting HIV-1 to Fc gamma R on human phagocytes via bispecific antibodies reduces infectivity of HIV-1 to T cells. 812 Apr 55

Major histocompatibility complex class II deficiency (bare lymphocyte syndrome) is a rare primary immunodeficiency disorder characterized by profound defects in human leukocyte antigen class II expression, inconsistent and incomplete expression of human leukocyte antigen class I molecules, and a complete lack of cellular and humoral immune responses to foreign antigens. To define the clinical and immunologic characteristics, outcome, and natural history of major histocompatibility complex class II deficiency, we retrospectively analyzed 30 consecutive patients. Clinical onset occurred in the first year of life, usually involving recurrent bronchopulmonary infections and chronic diarrhea. The clinical course was complicated by viral meningoencephalitis, hepatitis, cholangitis, and various autoimmune phenomena. Prognosis was very poor: the mean age at the time of death was 4 years. The main cause of death was overwhelming viral infection. Recent advances in bone marrow transplantation have raised hopes of curative treatment: 6 of 14 patients who underwent bone marrow transplantation were cured. Long-term survival after human leukocyte antigen-identical and haploidentical bone marrow transplantation seemed to depend primarily on the presence of preexisting viral infections.
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PMID:Major histocompatibility complex class II deficiency: clinical manifestations, immunologic features, and outcome. 822 25

The rate of progression to disease varies considerably among individuals infected with human immunodeficiency virus-type 1 (HIV-1). Analyses of semiannual blood samples obtained from six infected men showed that a rapid rate of CD4 T cell loss was associated with relative evolutionary stasis of the HIV-1 quasispecies virus population. More moderate rates of CD4 T cell loss correlated with genetic evolution within three of four subjects. Consistent with selection by the immune constraints of these subjects, amino acid changes were apparent within the appropriate epitopes of human leukocyte antigen class I-restricted cytotoxic T lymphocytes. Thus, the evolutionary dynamics exhibited by the HIV-1 quasispecies virus populations under natural selection are compatible with adaptive evolution.
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PMID:Adaptive evolution of human immunodeficiency virus-type 1 during the natural course of infection. 896 57

Host immunologic factors, including human immunodeficiency virus (HIV)-specific cytotoxic T lymphocytes (CTL), are thought to contribute to the control of HIV type 1 (HIV-1) replication and thus delay disease progression in infected individuals. Host immunologic factors are also likely to influence perinatal transmission of HIV-1 from infected mother to infant. In this study, the potential role of CTL in modulating HIV-1 transmission from mother to infant was examined in 11 HIV-1-infected mothers, 3 of whom transmitted virus to their offspring. Frequencies of HIV-1-specific human leukocyte antigen class I-restricted CTL responses and viral epitope amino acid sequence variation were determined in the mothers and their infected infants. Maternal HIV-1-specific CTL clones were derived from each of the HIV-1-infected pregnant women. Amino acid substitutions within the targeted CTL epitopes were more frequently identified in transmitting mothers than in nontransmitting mothers, and immune escape from CTL recognition was detected in all three transmitting mothers but in only one of eight nontransmitting mothers. The majority of viral sequences obtained from the HIV-1-infected infant blood samples were susceptible to maternal CTL. These findings demonstrate that epitope amino acid sequence variation and escape from CTL recognition occur more frequently in mothers that transmit HIV-1 to their infants than in those who do not. However, the transmitted virus can be a CTL susceptible form, suggesting inadequate in vivo immune control.
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PMID:Frequent detection of escape from cytotoxic T-lymphocyte recognition in perinatal human immunodeficiency virus (HIV) type 1 transmission: the ariel project for the prevention of transmission of HIV from mother to infant. 1019 93

Despite the conserved nature of the human immunodeficiency virus type 1 (HIV-1) gag gene, multiple quasispecies of the p24 gene coexist in HIV-1-infected patients. We cloned and sequenced 31 p24 genes from four HIV-1-infected patients. The intrapatient homology between the p24 genes ranged from 97.1 to 99.1%, whereas the interpatient homology ranged from 91.5 to 93.8%, suggesting a host-specific evolution. Synonymous and nonsynonymous nucleotide changes were evenly distributed in the p24 gene, with 27 and 28%, respectively, located within host human leukocyte antigen class I recognition sites. This would suggest only a minor influence from the host cytotoxic T-cell response on the evolution of the p24 gene. The importance of minor variations within p24 was analyzed by designing DNA-based immunogens from two distinct p24 quasispecies genes simultaneously derived from one patient. In plasmid-immunized H-2(b), H-2(d), and H-2(k) haplotype mice, a clear influence from the host major histocompatibility complex was noted on the immune responses, fully consistent with those noted when a recombinant p24 protein is used as the immunogen. The two p24 DNA immunogens did not differ in their immunogenicity, indicating that the limited genetic variability (<1%) had little influence on the immune responses.
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PMID:Variability and immunogenicity of human immunodeficiency virus type 1 p24 gene quasispecies. 1079 49

Carriers of certain human leukocyte antigen class I alleles show favorable prognosis of human immunodeficiency virus type 1 (HIV-1) infection, presumably due to effective CD8(+) cytotoxic T-lymphocyte responses, but close relationships between class I variants mediating such responses to natural and to vaccine HIV-1 antigen have not been established. During 6 to 30 months of administration and follow-up in trials of ALVAC-HIV recombinant canarypox vaccines, cells from 42% of 291 HIV-1-negative vaccinated subjects typed at class I loci responded to an HIV-1 protein in a lytic bulk CD8(+) cytotoxic T-lymphocyte assay. By 2 weeks after the second dose, higher proportions of vaccinees carrying one of two alleles consistently associated with slower progression of natural HIV-1 infection reacted at least once: B*27 carriers reacted to Gag (64%; odds ratio [OR] = 10.3, P = 0.001) and Env (36%; OR = 4.6, P = 0.04), and B*57 carriers reacted to Env (44%; OR = 6.6, P < 0.05). By 2 weeks after the third or fourth dose, B*27 carriers had responded (two or more reactions) to Gag (33%; OR = 4.4, P < 0.05) and B*57 carriers had responded to both Gag (39%; OR = 5.3, P = 0.013) and Env (39%; OR = 9.5, P = 0.002). Homozygosity at class I loci, although conferring an unfavorable prognosis following natural infection, showed no such disadvantage for vaccine response. Individual class I alleles have not previously demonstrated such clear and consistent relationship with both the clinical course of an infection and cellular immunity to a vaccine against the infectious agent. This proof of principle that class I an alleles modulate both processes has implications for development of HIV-1 and presumably other vaccines.
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PMID:Polymorphisms in HLA class I genes associated with both favorable prognosis of human immunodeficiency virus (HIV) type 1 infection and positive cytotoxic T-lymphocyte responses to ALVAC-HIV recombinant canarypox vaccines. 1150 13

Proteins may serve as ideal CD8(+) T cell immunogens for human immunodeficiency virus type 1 (HIV-1) if they can be delivered to and processed through the human leukocyte antigen class I pathway. This study shows that human blood monocyte-derived dendritic cells loaded with liposome-complexed HIV-1 proteins and matured with CD40 ligand can prime CD8(+) T cells to HIV-1 in vitro. Whole HIV-1 protein in liposome may be an effective immunogen for HIV-1 vaccine protocols.
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PMID:Priming of human immunodeficiency virus type 1 (HIV-1)-specific CD8+ T cell responses by dendritic cells loaded with HIV-1 proteins. 1255 58

Neuroblastoma (NB) is a pediatric extracranial tumor characterized by downregulation of human leukocyte antigen class I and defects of the antigen processing machinery, two features that make it an appropriate target for natural killer (NK)-mediated lysis. NKG2D is an activating immunoreceptor expressed by cytotoxic T lymphocytes and NK cells. The ligands for NKG2D are the major histocompatibility complex class I-related chain (MIC)A and MICB glycoproteins, and the UL-16-binding proteins (ULBPs). Here, the expression of NKG2D ligands was investigated in human primary NB tumors and cell lines because scanty information is available on this issue. MICA, MICB, and ULBP transcripts were found in most tumors and cell lines. MICA protein was detected in some NB cell lines but not in primary tumors. A soluble form of MICA (sMICA) was identified in most patient sera and in some cell line supernatants. sMICA downregulated surface NKG2D in normal peripheral blood CD8(+) cells and decreased NK-mediated killing of MICA(+) NB cells. MICB was detected exclusively in the cytosol of primary tumors and cell lines. Approximately 50% of primary tumors expressed ULBP-2, but not ULBP-1 or -3. ULBP-3 was expressed in 5 of 9 cell lines, ULBP-2 in 2 of 9, whereas ULBP-1 was never detected. These studies delineate novel potential pathways of tumor escape and immunodeficiency in NB.
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PMID:Downregulation and/or release of NKG2D ligands as immune evasion strategy of human neuroblastoma. 1554 65


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