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)

Homologous regions of five amino acids each, were identified in the NH2-terminal domain of human class II beta chains and the COOH terminus of HIV I envelope protein. The homologous regions are highly conserved among different DR and DQ alleles and also among different isolates of HIV. Septamers containing these sequences were synthesized and used for the generation of murine mAbs. The mAbs selected for this study were raised against the HIV I-derived peptide and reacted strongly not only with the immunizing peptide, but also with the homologous class II-derived peptide. These mAbs also reacted with native MHC class II antigens expressed on human B cell lines and on murine fibroblast L cell lines transfected with the genes coding for the alpha and beta chains of human class II antigens. Furthermore, sera from 36% of AIDS patients tested contained antibodies that reacted with the class II-derived peptide, as well as with intact class II molecule-rich cell extracts. Such antibodies in HIV I-infected individuals may recognize self class II antigens, triggering autoimmune mechanisms that could contribute to the development of immunodeficiency in AIDS patients.
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PMID:Identification of homologous regions in human immunodeficiency virus I gp41 and human MHC class II beta 1 domain. I. Monoclonal antibodies against the gp41-derived peptide and patients' sera react with native HLA class II antigens, suggesting a role for autoimmunity in the pathogenesis of acquired immune deficiency syndrome. 312 28

Blood monocytes were analyzed in 28 patients with chronic lymphocytic leukemia without previous cytotoxic therapy and without recent infection. Using monoclonal antibodies and flow cytometry, monocytes identified by LeuM3 or My4 were low in percentage (2.3%), but absolute numbers were increased in many patients with values exceeding the normal range (120 to 510/microliter) in seven of 28 patients. Monocytosis was more prominent in patients with high leukemic counts, but there was no correlation to clinical stages. Monocytopenia was evident with less than 50 LeuM3+ cells/microliter in three patients. Two-color fluorescence was used for the analysis of cell surface expression of major histocompatibility complex (MHC) Class II molecules, complement receptors, and Fc receptors on the LeuM3+ monocytes. Compared to cells from control donors, there was an increase for MHC class II antigens, complement receptors, and Fc receptors on the monocytes in chronic lymphocytic leukemia, in terms of both the percentage of positive cells among the LeuM3+ monocytes and of fluorescence intensity. This increase was not restricted to patients with monocytosis nor were the molecules always upregulated concomitantly. The increase of antigen expression on LeuM3+ monocytes was more than 50% (1.5-fold) in seven of 22 patients for MHC Class II antigens, in seven of 16 patients for complement receptor and in six of 12 patients for Fc receptor. A similar decrease of antigen expression was observed only in one patient for MHC Class II and in one patient for complement receptor expression. Monocytosis and increased expression of monocyte cell surface antigens described for a large portion of patients might be causally involved in the immunodeficiency in chronic lymphocytic leukemia.
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PMID:Abnormal blood monocytes in chronic lymphocytic leukemia. 340 22

One hundred and eighty-four serum specimens were assayed for antibodies to the human immunodeficiency virus. All specimens were screened with a commercial enzyme immunoassay and confirmed by two indirect immunofluorescence assays. Sera were also assayed by Western blot. Results from sera of 48 healthy heterosexual volunteers were all negative by EIA, IFA, and Western blot. Sera from 50 healthy homosexual men negative by EIA were also negative by IFA and Western blot. Sixty-two patients with persistent generalized lymphadenopathy or newly diagnosed AIDS all were positive by EIA, IFA, and Western blot. Of 24 sera from patients with autoantibodies, with no evidence of AIDS-related diseases, five appeared to be false-positive by EIA, since they were nonreactive by IFA and Western blot. In addition, three other samples contained both autoantibodies and human immunodeficiency virus antibodies. False-positive results were observed in both the EIA and IFA with monoclonal antibodies directed toward the MHC class II antigens DQ and DR. The reactivity of these antibodies could not be distinguished from positive patients' sera, in either EIA or IFA. We conclude that in general indirect immunofluorescence performed well as a confirmatory test after screening by enzyme immunoassay for human immunodeficiency virus antibodies.
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PMID:Evaluation of the indirect immunofluorescence assay as a confirmatory test for detecting antibodies to the human immunodeficiency virus. 353 56

Humans and domestic animals with African trypanosomiasis exhibit abnormalities of immune function characterized by polyclonal lymphocyte activation and, paradoxically, progressive immunodeficiency. Mice infected with Trypanosoma brucei clone IaTat1.2 develop a fulminant parasitemia by day 5 of infection. B lymphocytes isolated from spleens of infected mice display an aberrant activation phenotype manifested by decreased CD23 and surface IgM, increased CD69 and L-selectin, and normal levels of surface IgD, MHC class II, CD32, and transferrin receptor. Kinetic analyses showed that CD23 and surface IgM were continuously down-regulated from day 2 through day 5, whereas MHC class II was elevated on days 2 and 3, but returned to normal levels by day 5, suggesting that CD23 and MHC class II are independently regulated in T. brucei infection. The aberrant activation phenotype of B cells responding in vivo to T. brucei was accompanied by impaired responsiveness of these B cells to mitogenic stimulation in vitro. The pathologic phenotypic and functional properties of B lymphocytes from T. brucei-infected mice can be partially accounted for by the virtual total arrest of B cells in G0/G1A of the cell cycle. The B lymphocyte alterations observed in the present studies provide new insight into the immunopathology of African trypanosomiasis. We propose that terminal infection with T. brucei induces early activation events in host B lymphocytes, but that the activation response becomes aberrant by the development of what seems to be a total block in cell cycle progression.
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PMID:B lymphocytes of mice display an aberrant activation phenotype and are cell cycle arrested in G0/G1A during acute infection with Trypanosoma brucei. 751 10

To increase the inherently weak immunogenicity of synthetic peptide vaccines, we used recombinant DNA techniques to generate chimeras between immunogenic determinants of human immunodeficiency virus type 1 (HIV-1) gp120 and antibody Fab fragments reactive with surface structures displayed specifically on human antigen-presenting cells (APCs), including surface immunoglobulin D (sIgD) and class II major histocompatibility complex (MHC) molecules. Hybridomas producing anti-human MHC class II (HLA-DR) or surface immunoglobulin D monoclonal antibodies (MAbs) that recognize nonpolymorphic determinants were used to clone chimeric Fab gene fragments by employing an established procedure to generate antigen-binding Fab libraries in phagemid vector pComb3. Molecular and immunochemical analysis indicated that the expected chimeric Fab fragments expressing the HIV-1 epitopes were correctly cloned and expressed in Escherichia coli and retained the binding specificity of the native (hybridoma-derived) MAb. The chimeric Fab fragments targeted the linked HIV-1-derived antigenic determinants to the surface of human APCs in vitro, as evidenced by fluorescence-activated cell sorter analysis. Furthermore, such recombinant immunotargeted HIV-1 peptide antigens demonstrated improved immunogenicity over equivalent nonimmunotargeted control antigens, as shown by their ability to stimulate interleukin-2 production by CD4+ T-helper cells from human donors exposed to HIV-1 antigens. These data suggest that immunotargeting of recombinant peptide antigens via the attached Fab fragments facilitates uptake by human APCs with subsequent access to the MHC class II processing pathway, thereby validating the immunotargeting concept for such recombinant subunit vaccines in an in vitro human system.
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PMID:Immunogenic targeting of recombinant peptide vaccines to human antigen-presenting cells by chimeric anti-HLA-DR and anti-surface immunoglobulin D antibody Fab fragments in vitro. 753 57

CD4 is the predominant cell membrane protein that binds human immunodeficiency virus type 1 (HIV-1) gp120 and facilitates HIV-1 infection, but other membrane-associated molecules may be involved in determining HIV-1 cellular infection. Our prior work had suggested that CD44, the transmembrane receptor for hyaluronan, might play a role in the infection of mononuclear phagocytes with HIV-1. In the present work, we have used cells of the CD4-positive, CD44-negative human T-lymphoblast cell line Jurkat to study the role of CD44 in HIV-1 infection and tropism. Cells were transfected with cDNA for the standard (S, or hematopoietic) CD44 isoform CD44S or the epithelial isoform CD44E. The resultant lines expressed appropriate CD44S or CD44E mRNA and protein. While the parent Jurkat cells, those transfected with vector alone, and those transfected with CD44E could be productively infected with only the lymphocytotropic strain HIV-1-LAI, cells transfected with CD44S were rendered susceptible to productive infection with the monocytotropic strains HIV-1-BaL and HIV-1-ADA. Also, CD44S-transfected cells displayed higher levels of infection with HIV-1-LAI than did the other transfected Jurkat cells. The transfected cell line cells all had comparable growth rates and expressed similar levels of the membrane antigens CD4, CD7, major histocompatibility complex (MHC) class I, MHC class II, and CD11a, while levels of CD3 were slightly higher in cells transfected with vector alone and in one of the clones transfected with CD44S. Hyaluronan binding was increased in cells transfected with either CD44S or CD44E. Mouse NIH 3T3 fibroblasts transfected with human CD4, human CD44S, or both human CD4 and CD44S displayed the appropriate antigens, but they could not be productively infected with lymphocytotropic or monocytotropic strains of HIV-1. The results indicate that in human leukocytes, CD44S is an important determinant of HIV-1 productive infection and may be involved in viral cellular tropism.
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PMID:Cellular CD44S as a determinant of human immunodeficiency virus type 1 infection and cellular tropism. 753 3

Major histocompatibility complex (MHC) class II molecules are heterodimeric cell surface proteins that are critically important for the development and function of cells in the immune system. In particular, the maturation of CD4+ T cells is dependent on the expression of MHC class II molecules on thymic epithelium, while the activation of these cells requires the expression of class II molecules on specialized antigen-presenting cells in the periphery. The importance of class II molecules is especially evident in humans who are afflicted with MHC class II-deficient combined immunodeficiency, as these individuals die at an early age unless provided with a bone marrow transplant. Here we discuss the functional consequences of MHC class II deficiency in a mouse model generated by gene targeting in embryonic stem (ES) cells. These mice have proved to be valuable reagents for dissecting the mechanisms by which MHC class II molecules control the maturation and activation of lymphocytes as well as for elucidating the role of these cells in various immune responses.
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PMID:Immune responses in MHC class II-deficient mice. 761 30

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)
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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

Infection of dendritic cells (DC) by human immunodeficiency virus (HIV) has been disputed. Employing a fluorescence-activated cell sorter, DC, identified by the absence of membrane markers for T, B, natural killer (NK) and monocytic cells and by high levels of MHC class II DR antigen, were shown to express low levels of CD4. Immunomagnetic beads were used to separate blood low density cells, which are enriched for DC, into CD4-positive and -negative populations. Examination of these cells by electron microscopy showed an increase in the percentage of cells with DC morphology in the CD4-positive fraction and a reduction in the CD4-negative fraction. Electron microscopy of semi-purified DC preparations infected in vitro for 5 days with HIV-1 revealed morphologically distinct veiled DC with mature virions on the cell surface and virus budding through the cell membrane. Further evidence for the growth of HIV in DC was provided by experiments in which DC were extensively depleted of contaminating lymphocytes and monocytes prior to infection. Estimation of provirus load by a nested PCR indicated that after 5 days an infection level of one provirus copy per five cells could be achieved. After 7 days the provirus copy number could exceed the cellular genome copy number, suggesting that some cells had more than one provirus. Infectious virus could not be demonstrated in these cultures after 24 h but was detected after 5 or 7 days. Infection of DC in the presence of antibodies against CD4 was inhibited and suggests infection occurs via a CD4-dependent pathway. These results confirm that DC are susceptible to HIV infection in vitro. The immunological consequences of DC infection in vivo may be significant in the pathogenesis of AIDS.
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PMID:CD4 expression on dendritic cells and their infection by human immunodeficiency virus. 773 Jul 99

Murine mammary tumour viruses (MMTVs) are retroviruses that encode superantigens capable of stimulating T cells via superantigen-reactive T cell receptor V beta chains. MMTVs are transmitted to the suckling offspring via the milk. We have established that class II and B cell-deficient mice that were foster nursed by virus-secreting mice do not transfer infectious MMTVs to their offspring. No MMTV proviruses could be detected in the spleen and mammary tissue of these mice and there was no deletion of MMTV superantigen-reactive T cells. These results confirm that superantigen expression in the context of MHC class II molecules is required for MMTV transmission. We conclude that B cells are essential for the completion of the viral life cycle in vivo. This indicates that B cells are infected first and that viral amplification takes place only if infected B cells present the MMTV superantigen on their surface which, in turn, results in activation of T cells expressing the appropriate T cell receptor V beta chains. These activated T cells stimulate B cells which enables viral replication. Human T cells carry all the structural features required for an efficient response to murine retrovirally encoded superantigens. Superantigen-like stimulation of human T cells has been demonstrated in both infectious and autoimmune diseases. Human immunodeficiency virus may encode a superantigen but this has not been proven.
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PMID:The role of superantigens in the immunobiology of retroviruses. 779 68


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