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 have identified several immunoreactive epitopes on the human immunodeficiency virus (HIV) type 1 transmembrane envelope protein by synthesizing various regions of the protein as fusions to the trpE gene in Escherichia coli. Ten fusion clones which expressed overlapping peptides were found to contain epitopes reactive with antibodies in sera of North American (NAm) and West African (WAf) patients with acquired immune deficiency syndrome (AIDS). An immunodominant epitope which reacted with all HIV-infected patients' sera was mapped to a 51-amino acid sequence in the N terminus of p41. A novel epitope was also identified in the C terminus of p41 which was reactive with 41% and 48% of the sera tested from NAm and WAf, respectively. In addition, several minor epitopes were identified. We observed that sera from WAf reacted more strongly to minor HIV-1 p41 epitopes than did sera from similarly infected individuals in NAm. We also report on the detection of antibodies from patients with HIV-2 infection in WAf which cross react with HIV-1 p41 recombinant envelope antigens.
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PMID:Characterization of immunoreactive epitopes of the HIV-1 p41 envelope protein using fusion proteins synthesized in Escherichia coli. 245 55

Freshly separated unfractionated peripheral blood mononuclear cells (PBMC) and cloned cell lines from a healthy human immunodeficiency virus 1 (HIV-1)-seropositive individual were examined for cytotoxic responses to HIV proteins expressed by recombinant vaccinia viruses. It was found that freshly isolated PBMC recognize variant envelope proteins of HIV-1 but not a more distantly related envelope protein derived from the simian immunodeficiency virus (SIVmac). Although the effector cells were predominantly CD8+, both MHC-matched and -unmatched target cells were lysed. Cytotoxic T lymphocyte (CTL) clones were found to lyse cells expressing HIV-1 envelope or reverse transcriptase. In contrast to the cytotoxic response detected with PBMC, the cloned CTLs were major histocompatibility complex (MHC) class I restricted. Our finding that a cloned CTL line lysed cells expressing highly divergent HIV envelopes strongly suggested that a conserved epitope was recognized. Identification of these shared epitopes may assist in designing a vaccine for HIV-1 that could stimulate MHC-restricted cytotoxic responses.
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PMID:Group-specific, major histocompatibility complex class I-restricted cytotoxic responses to human immunodeficiency virus 1 (HIV-1) envelope proteins by cloned peripheral blood T cells from an HIV-1-infected individual. 246 Aug 73

Studies are presented here which demonstrate that antibodies reacting with human interleukin-2 (IL-2) are present in the sera of patients infected with the human immunodeficiency virus (HIV). It is likely that these antibodies are present due to a homology between the HIV envelope protein and IL-2. The homologues are six amino acids in length corresponding to the carboxy terminus of gp41, Leu-Glu-Arg-Ile-Leu-Leu (LERILL), and residues 14-19 of secreted IL-2, Leu-Glu-His-Leu-Leu-Leu (LEHLLL). Thus, we questioned whether antibodies made against this HIV envelope peptide would cross-react with IL-2. Not only do a high percentage of the HIV-infected individuals tested here have antibodies against LERILL, but these antibodies cross-react with the IL-2 sequence, LEHLLL. Additional antigenic processing of IL-2 is suggested by the finding that epitopes other than this sixmer are also recognized by antibodies in patients' sera. Thus, these studies suggest a mechanism by which infection with HIV can induce a potentially suppressive autoimmune response. Specifically, antibodies against an HIV envelope peptide cross-react with an epitope in IL-2.
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PMID:Individuals infected with HIV possess antibodies against IL-2. 246 43

Several gene fusions have been constructed in which coding sequences for antigenic regions of the pre-S sequences of hepatitis B virus, hepatitis B surface antigen, and the envelope protein of human immunodeficiency virus were linked to the 3' end of that for the first 144 residues of hepatitis B core antigen. The sequences were expressed efficiently in Escherichia coli to give stable products that assembled to form particles morphologically similar to hepatitis B core antigen itself. The products exhibited the antigenic and immunogenic characteristics of both the hepatitis B core antigen epitopes and the epitopes carried by the additional sequences, thus illustrating the value of such proteins as immunological reagents and potential vaccines.
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PMID:Immunogenicity of peptide fusions to hepatitis B virus core antigen. 247 30

The present study demonstrates that maternal antibodies to certain epitopes of human immunodeficiency virus 1 (HIV-1) proteins are associated with a defined outcome for at-risk pregnancies of HIV-infected women. An initial retrospective analysis of antibodies to synthetic peptides and recombinant proteins representing env, pol, and gag regions of HIV-1 was carried out. Sera studied were from 33 children who were born to HIV-infected mothers and whose clinical outcome was known at the time of analysis. Sera, collected within the first 6 months of life, of uninfected at-risk children were found to selectively contain maternal antibodies to certain peptides containing epitopes of the HIV envelope glycoprotein gp120. To confirm the predictive role of maternal antibodies to defined HIV-1 epitopes, a prospective analysis was then performed on sera from 21 HIV-seropositive mothers and their infants, whose clinical and immunological status was then followed up for a period of at least 15 months. As expected, antibodies to the same envelope protein peptides were detected almost exclusively in sera from mothers of uninfected children. Our data suggest that antibodies against select epitopes of HIV envelope protein gp120 might play an important role in preventing mother-to-child transmission of HIV-1 infection. Accordingly, site-directed serology might be used to predict the outcome of an at-risk pregnancy of an HIV-infected woman.
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PMID:Presence of maternal antibodies to human immunodeficiency virus 1 envelope glycoprotein gp120 epitopes correlates with the uninfected status of children born to seropositive mothers. 247 14

Insertion of foreign oligopeptide sequences (40-50 amino acids in length) into the Pro144 position of hepatitis B core antigen (HBcAg) leads to the formation of chimeric capsids in Escherichia coli cells. These capsids are morphologically and immunologically similar to native HBcAg, but expose the inserted oligopeptides on their outer surface and exhibit antigenic and immunogenic characteristics of the latter. As a source of model antigenic determinants, the appropriate DNA copies excised from cloned viral genes such as the pre-S region of hepatitis B virus, the transmembrane protein gp41 of human immunodeficiency virus 1 and the envelope protein gp51 of bovine leukemia virus have been used. The localization of the inserted antigenic determinants on the surface of chimeric capsids does not depend on the presence or absence of the arginine-rich, 39 amino acid-long C terminus of HBcAg.
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PMID:Recombinant core particles of hepatitis B virus exposing foreign antigenic determinants on their surface. 248 Sep 17

Helper T cell determinants should be an important component of an anti-human immunodeficiency virus (HIV) vaccine aimed at either antibody or cytotoxic T cell immunity. However, model protein studies have raised concern about the usefulness of any single determinant, because a given determinant is likely to be seen by only a small subset of major histocompatibility complex (MHC) types within the population. Here, we use 44 peptides, including ones predicted and not predicted on the basis of amphipathicity to be potential T cell sites, to locate T cell antigenic determinants recognized by mice of four MHC haplotypes immunized with the whole gp 160 envelope protein. Although the preselection of peptides necessitates caution in a statistical analysis, alpha-amphipathic peptides predominated among sites eliciting the strongest response. Although we have not tested the entire sequence, we have identified six multideterminant regions, in which overlapping peptides are recognized by mice of either three or all four MHC types. Four of the six regions have sequences relatively conserved among HIV-1 isolates. The existence of such multideterminant regions recognized by multiple MHC haplotypes suggests the possibility that use of peptides longer than a minimal determinant and containing several overlapping determinants may be a possible approach to circumvent the serious problem of MHC restriction in peptide vaccines aimed at eliciting T cell immunity.
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PMID:T cell multideterminant regions in the human immunodeficiency virus envelope: toward overcoming the problem of major histocompatibility complex restriction. 248 61

Human immunodeficiency virus (HIV) p24 antigenemia was assessed in a longitudinal study of 52 homosexual men who developed serum antibody to HIV. Antibody seroconversion to HIV as defined by a positive HIV enzyme immunoassay (EIA) confirmed by Western (immuno-) blot was associated with three major patterns of HIV antigenemia. In the first pattern, a transient antigenemia was noted 6 (six subjects) and 12 (one subject) months prior to detection of antibody by HIV EIA and Western blot in 7 (13.5%) of the 52 men. Use of an EIA employing a recombinant envelope protein (ENV9) was able to detect antibody in four of these seven men at the time of this early antigenemia. In the second pattern, HIV p24 antigenemia occurred in 8 (15.4%) of the 52 subjects within the first 12 months after HIV antibody seroconversion. No p24 antigen was detected in the 37 (71.1%) remaining subjects. CD4+ cell numbers were lower in antigen-positive men before and after antibody seroconversion. Development of acquired immunodeficiency syndrome (AIDS) or AIDS-related complex was strongly associated with evidence of persistent p24 antigenemia during the early, postseroconversion period. HIV p24 antigenemia may be of value in determining appropriate cohorts for drug therapy trials for subjects with early-phase HIV infection.
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PMID:Association of human immunodeficiency virus (HIV) p24 antigenemia with decrease in CD4+ lymphocytes and onset of acquired immunodeficiency syndrome during the early phase of HIV infection. 250 52

T lymphocytes from mice and healthy humans immunized against the human immunodeficiency virus (HIV) envelope have recently been shown to recognize two antigenic regions of the gp160 HIV-envelope protein which have been located on the basis of amphipathicity. In HIV-infected humans, T-cell proliferative responses are lost soon after infection. Here we demonstrate that interleukin-2 production is often retained even when proliferative activity is absent, and that it can be used to monitor T-helper cell responses by HIV-seropositive donors. We use this approach to investigate the T-helper cell response of 42 asymptomatic HIV-seropositive patients to four synthetic gp160 peptides and to influenza A virus, an antigen requiring intact CD4 T-helper cell function. As many as 67% of the HIV-seropositive donors who retain responsiveness to influenza A virus respond to a single peptide, and 85-90% responded to at least one of the peptides.
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PMID:Interleukin-2 production used to detect antigenic peptide recognition by T-helper lymphocytes from asymptomatic HIV-seropositive individuals. 252 68

The envelope glycoprotein (gp70) of a molecularly cloned, replication-defective feline leukemia virus (FeLV-FAIDS clone 61C) carries determinants for induction of fatal immunodeficiency disease, whereas the gp70 of its companion replication-competent, probably parent virus (clone 61E) does not. Immunoprecipitation analysis of the extracellular glycoproteins of 61E and EECC, a replication-competent viral construct composed of the 61C env and 3' long terminal repeat fused to the 61E gag-pol genes, demonstrated that the gp70 of EECC could be distinguished from that of 61E by both feline immune serum and a murine monoclonal antibody. Molecular weights of both the envelope precursor polyprotein (gp80) and the mature extracellular glycoprotein (gp70) of 61E were smaller than the corresponding proteins from the pathogenic EECC. Both the molecular weight disparity and monoclonal antibody discrimination of the two gp80s were abolished by inhibition of envelope protein glycosylation with tunicamycin, whereas the apparent gp70 size differences were resolved by enzymatic removal of N-linked oligosaccharides. Pulse-chase studies in EECC-infected cells demonstrated that processing of gp80 to gp70 was delayed and that this retardation of envelope glycoprotein processing could be simulated in 61E-infected cells by treatment with the glucosidase inhibitor N-methyldeoxynojirimycin, a compound that causes retention of oligosaccharides in the high-mannose form. The resultant 61E gp70 then could be recognized by sera from EECC-immunized cats. The presence of a higher content of sialic acid on the apathogenic 61E gp70 indicated that oligosaccharides of 61E and EECC gp70 were processed differently. These data suggested that the unique biochemical properties which distinguish the envelope glycoproteins of the FeLV-FAIDS variant from its companion apathogenic parent virus were responsible for T-cell cytopathicity and induction of immunodeficiency disease. Further biochemical characterization of these glycoproteins should be useful in understanding the pathogenic mechanisms of immunodeficiency disease induced by retroviruses.
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PMID:Posttranslational modifications distinguish the envelope glycoprotein of the immunodeficiency disease-inducing feline leukemia virus retrovirus. 253 25


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