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

Adenovirus type 35 (Ad35) is a group B adenovirus that has been isolated primarily from patients with acquired immunodeficiency syndrome and other immunodeficiency disorders. We have studied the interaction of this unique adenovirus with the immune system by analyzing Ad35 early viral proteins in infected HeLa cells. We have identified a 29,000-Mr Ad35 early glycoprotein, E29, which associates with class I antigens of the major histocompatibility complex (MHC) in the endoplasmic reticulum. Ad35 E29 is analogous to the group C Ad2 early glycoprotein E3-19K (E19), which has been shown to interfere with the expression of class I antigens on the cell surface (H. Burgert and S. Kvist, Cell 41:987-997, 1985). In contrast to the Ad2 glycoprotein, Ad35 E29 was synthesized in much smaller amounts, was more extensively glycosylated, and did not cross-react with polyclonal antibody against the Ad2 protein. As a control, a class I antigen-binding glycoprotein from another group B adenovirus, Ad7, was also characterized and was found to have properties similar to those of Ad35 E29. Therefore, the differences in the glycosylation and quantity of class I antigen-binding glycoproteins between Ad35 and Ad2 are group related. Inhibition of the expression of MHC class I antigens, which are needed for cytotoxic-T-lymphocyte recognition of virus-infected cells, appears to play a vital role in the adenovirus life cycle in vivo. Our data indicate that this function has been conserved despite significant differences in the MHC class I antigen-binding glycoprotein and in the pathogenicity between serotypes.
 ...
PMID:Characterization of a major histocompatibility complex class I antigen-binding glycoprotein from adenovirus type 35, a type associated with immunocompromised hosts. 296 Aug 30

The target antigen of the FN18 monoclonal antibody, called RhT3, is probably the rhesus monkey homologue of the human CD3 antigen, expressed on mature T cells. RhT3 appears to be polymorphic, since FN18 was not reactive with T cells from all the screened animals. Thus, immunofluorescent staining of peripheral blood lymphocytes with FN18 antibody revealed either a positive or a negative phenotype for the target antigen. In a rhesus monkey population, nonreactivity for FN18 was observed in low frequency (2.7%). Expression and non-expression of RhT3 appeared to be constant characteristics. Non-expression was not associated with any demonstrable immunodeficiency. Further, there seemed to be no association between the presence of the FN18 target antigen and sex, age or expression of MHC class I antigens. Family studies indicated that the positive phenotype is expressed in the same fashion by animals presumably heterozygous or homozygous for the positive allele, the negative phenotype being expressed only on cells from animals homozygous for an assumed blank allele. Therefore, the positive phenotype is likely to be transmitted in an autosomal dominant mode. In the animals with the negative phenotype, normal T-cell numbers were present, as was demonstrated by B- and T-cell specific monoclonal antibodies. Cytoplasmic staining of cytospun lymphocyte preparations with FN18 revealed that polymorphism was present at the intracellular level. Cell proliferation tests, using PWM and Con A as mitogens, showed the presence of apparently functional RhT3 cell surface molecules in FN18 non-reactive animals. Polymorphism is therefore assumed to be at the epitope level.
 ...
PMID:Polymorphism for RhT3, a CD3-like cell surface antigen, expressed on rhesus monkey T lymphocytes. 310 Apr 38

In the classic model of antigen processing and presentation, viral antigens must be synthesized within the cytoplasm of infected cells to be processed and presented to CD8+, MHC class I-restricted cytotoxic T lymphocytes (CTLs). We have examined the utility of a retroviral vector (pNeoNef) expressing the human immunodeficiency virus type (HIV-1)Lai Nef protein for the development of target cells to study HIV-specific CTLs. Autologous Epstein-Barr-transformed B cell lines (EBV-B cells) transduced with pNeoNef were efficiently lysed by CTL lines from donors capable of lysing EBV-B cells infected with a recombinant vaccinia virus (rVV) expressing Nef. Also, the transduced cells were efficient stimulator cells for the generation of Nef-specific CTL lines. The CTL lines thus generated recognized the same epitopes as CTL lines from the same donor generated by nonspecific stimulation. The use of similar cell lines transduced with retroviral vectors expressing HIV proteins may be useful in the study of CTLs in HIV-infected donors and in the study of the ability of candidate vaccines, including rVV, to induce HIV-specific CTLs. As antigen-presenting cells, the cell lines may be useful in the generation of antigen-specific CTL lines.
 ...
PMID:Efficient antigen presentation to cytotoxic T lymphocytes by cells transduced with a retroviral vector expressing the HIV-1 Nef protein. 751 96

The safety and the immunogenicity of a recombinant canarypox live vector expressing the human immunodeficiency virus type 1 (HIV-1) gp160 gene from the MN isolate, ALVAC-HIV (vCP125), followed by booster injections of a soluble recombinant hybrid envelope glycoprotein MN/LAI (rgp160), were evaluated in vaccinia-immune, healthy adults at low risk for acquiring HIV-1 infection. Volunteers (n = 20) received vCP125 (10(6) TCID50) at 0 and 1 month, followed randomly by rgp160 formulated in alum or in Freund's incomplete adjuvant (FIA) at 3 and 6 months. Local and systemic reactions were mild or moderate and resolved within the first 72 hr after immunization. No significant biological changes in routine tests were observed in any volunteer. Two injections of vCP125 did not elicit antibodies. Neutralizing antibodies (NA) against the HIV-1 MN isolate were detected in 65 and 90% of the subjects after the first and the second rgp 160 booster injections, respectively. Six months after the last boost, only 55% were still positive. Seven of 14 sera with the highest NA titers against MN weakly cross-neutralized the HIV-1 SF2 isolate; none had NA against the HIV-1 LAI or against a North American primary isolate. Specific lymphocyte T cell proliferation to rgp 160 was detected in 25% of the subjects after vCP125 and in all subjects after the first booster injection and 12 months after the first injection. An envelope-specific cytotoxic lymphocyte activity was found in 39% of the volunteers and characterized for some of them as CD3+, CD8+, MHC class I restricted. The adjuvant formulation did not influence significantly the immune responses.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:A prime-boost approach to HIV preventive vaccine using a recombinant canarypox virus expressing glycoprotein 160 (MN) followed by a recombinant glycoprotein 160 (MN/LAI). The AGIS Group, and l'Agence Nationale de Recherche sur le SIDA. 759 71

In view of the importance of cell-associated virus in AIDS virus transmission, an HIV vaccine should be able to induce a virus-specific CTL response. Traditional subunit vaccines have not elicited virus-specific CD8+ MHC class I-restricted CTL. We have used the simian immunodeficiency virus of macaques (SIVmac)/rhesus monkey model to explore the use of CTL epitope peptide-helper peptide conjugates for the vaccine elicitation of AIDS virus-specific CTL. We found that both the CTL epitope peptide-helper peptide conjugate and the CTL epitope peptide alone, when delivered in an emulsion with IFA, induced CTL epitope-specific CD8+ MHC class I-restricted CTL. These effector cells recognized processed viral protein and were readily cloned from PBL of the immunized monkeys. Moreover, the cloned effector cells inhibited SIVmac replication in PBL. Immunization with the CTL epitope peptide used in this study also elicited a CD4+ PBL proliferative response, suggesting that the peptide also contained a helper epitope. These studies provide further evidence for the potential usefulness of peptide-based AIDS virus vaccines.
 ...
PMID:Synthetic peptide in mineral oil adjuvant elicits simian immunodeficiency virus-specific CD8+ cytotoxic T lymphocytes in rhesus monkeys. 769 65

Major histocompatibility complex (MHC) class II deficiency is an inherited autosomal recessive combined immunodeficiency. The disease is known as bare lymphocyte syndrome (BLS). BLS is characterized by a lack of constitutive MHC class II expression on macrophages and B cells as well as a lack of induced MHC class II expression on cells other than professional antigen-presenting cells (APCs) due to the absence of mRNA and protein of the human leukocyte antigen (HLA) class II molecules, designated HLA-DR, -DQ, and -DP. The defect in gene expression is located at the transcriptional level and affects all class II genes simultaneously. Here we have analyzed transcription and protein expression of class II antigens in Epstein-Barr virus (EBV)-transformed B lymphoblastoid cell lines and mononuclear cells (MNCs) of twin brothers. Whereas flow cytometric analysis failed to detect class II antigens on the cell surface of the patients' EBV-B cells and MNCs, examination of the genes coding for HLA-DR, -DQ, -DP, and the invariant chain (Ii) by reverse transcriptase-polymerase chain reaction amplification resulted in an unusual mRNA pattern in the B cell lines of the patients (HLA-DR alpha +, -DR beta, -DQ alpha +, -DQ beta -, -DP alpha -; -DP beta +, Ii+). In accordance with these findings no HLA-DR beta-specific protein was detected by immunoblotting, whereas low levels of HLA-DR alpha and normal levels of Ii were present. In contrast to EBV-B cells, the MNCs of both patients displayed a residual HLA-DR beta, -DQ beta, and -DP alpha mRNA signal. Furthermore, HLA-DR beta-specific protein was found in addition to HLA-DR alpha by immunoblotting of cell lysates, even though it was clearly decreased as compared with controls. Our results indicate that the defect in class II antigen expression is not necessarily present to the same extent in B cells and cells of other lineages. mRNA levels of HLA-DR beta were found to be enriched in adherent cells within the MNC fraction. Further investigations indicated that the MHC class II expressed is functional in antigen presentation, as the two boys' CD4+ T cells became activated and expressed interleukin-2R after stimulation of peripheral blood mononuclear cell cultures with recall antigen (tetanus toxoid). Furthermore, T cells tested in one of the two patients responded to both MHC class I and II allostimulation, and this response was inhibited by monoclonal antibodies of the respective specificity.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Molecular characterization of major histocompatibility complex class II gene expression and demonstration of antigen-specific T cell response indicate a new phenotype in class II-deficient patients. 769 27

We have previously reported the induction of MHC class I-restricted, CD8+ cytotoxic T lymphocytes (CTLs) specific to human immunodeficiency virus type 1 (HIV-1) in mice by a 15-amino acid peptide (R15K) from the V3 loop in gp120. We now present evidence showing that CTL activity induced by R15K was stable for 8-10 weeks after a single injection and that as little as 20 micrograms peptide was sufficient for efficient CTL induction in vivo. While induction of CTLs was efficient with R15K emulsified in either complete or incomplete Freund's adjuvant, only a low-level CTL response was observed in mice immunized with R15K in either alum or saline. We analyzed a series of carrier-free synthetic peptides ranging in length from 8 to 24 amino acids from the V3 loop region and observed that peptide R10I consisting of 10 amino acids from the middle portion of R15K was more efficient for CTL induction. Additionally, lymph node cells from mice immunized with 24 and 15 amino acid peptides (N24G and R15K, respectively) when restimulated in vitro with R10I exhibited greater HIV-1 env-specific CTL activity than when either of the longer peptides was used for restimulation. A peptide consisting of only 8 amino acids (R8K) was sufficient neither for inducing primary CTLs nor for in vitro restimulation of lymph node CTL precursors. These results establish that a carrier-free 10-amino acid synthetic peptide from the V3 loop region in HIV-1 gp120 has the optimal sequence for efficient induction of HIV env-specific CTLs in mice.
 ...
PMID:Studies on in vivo induction of HIV-1 envelope-specific cytotoxic T lymphocytes by synthetic peptides from the V3 loop region of HIV-1 IIIB gp 120. 772 83

Because of the importance of the envelope glycoprotein (Env) in determining the pathogenicity of HIV-1 and the importance of the immune response to Env in controlling virus spread, attempts are being made to study HIV-1 Env-directed immunity in primate models. To date HIV-1 Env-specific effector T lymphocyte responses have not been demonstrated in virus-infected nonhuman primates. We have previously reported that cynomolgus monkeys can develop a persistent infection with a chimeric simian-human immunodeficiency virus (SHIV) composed of SIVmac239 carrying the HIV-1 env, tat, rev, and vpu genes. We now demonstrate that SHIV-infection of another macaque species, the rhesus monkey, generates persistent, HIV-1 Env-specific cytolytic T lymphocyte (CTL) responses. These CTL are CD8+ and major histocompatibility complex (MHC) class I-restricted. The induction of CTL was correlated neither to the virus load nor to the MHC class I haplotypes of the monkeys. The SHIV-infected rhesus monkey can, therefore, now be employed for studying effector T lymphocyte recognition of HIV-1 Env.
 ...
PMID:Human immunodeficiency virus type 1 envelope glycoprotein-specific cytotoxic T lymphocytes in simian-human immunodeficiency virus-infected rhesus monkeys. 774 49

We have developed a unique multiple step procedure to inactivate human immunodeficiency virus chemically with a very high safety margin while retaining antigenically active structural virion proteins, including gp120, in the final immunogen. The whole virus preparation (1-10 micrograms per dose) was highly immunogenic in a variety of small mammals and induced antibodies that recognized homologous and heterologous strains of HIV-1. Sera from immunized animals bound to peptides representing the entire sequence of the external glycoprotein gp120. Neutralizing antibodies active against the homologous immunizing strain and against heterologous HIV-1 strains were also elicited. Sera with virus neutralizing activity did not bind to MHC class I proteins derived from the human cell line used to grow the virus.
 ...
PMID:An experimental chemically inactivated HIV-1 vaccine induces antibodies that neutralize homologous and heterologous viruses. 776 78

Inclusion body myositis developed in two men, 36 and 48 years old with long-standing common variable immunodeficiency. Immunophenotypic analysis of the endomysial cells showed an increased number of natural killer (NK) cells (defined as CD57+, CD56+, CD3-, CD8-, CD68-) accounting for 8.5 to 9.5% of the total cells, compared with a mean of 1% in sporadic inclusion body myositis. The remaining cells were CD8+, macrophages, and CD4+ T cells. NK cells were positive for intercellular cell adhesion molecule-1 and invaded muscle fibers negative for major histocompatibility complex (MHC) class I. In contrast to ubiquitous endomysial expression of MHC class I antigen in sporadic inclusion body myositis, the MHC class I in common variable immunodeficiency and inclusion body myositis was absent or weakly expressed in only some of the muscle fibers surrounded by CD8+ cells. Enteroviral or retroviral RNA sequences were not amplified. Treatment with intravenous immunoglobulin improved strength in 1 patient whose repeated muscle biopsy specimen showed normal NK cells. We conclude that inclusion body myositis can develop in patients with common variable immunodeficiency. Common variable immunodeficiency with inclusion body myositis is an immune myopathy mediated by NK cells in a non-MHC class I-restricted cytotoxicity, and by CD8+ cells in an MHC class I-restricted process. This is the first description of an inflammatory myopathy in which NK cells participate in the myocytotoxic process.
 ...
PMID:Common variable immunodeficiency and inclusion body myositis: a distinct myopathy mediated by natural killer cells. 777 55


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>