Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

AIDS dementia complex is a common neurologic disorder in later stages of HIV-1 infection. Because virus-specific CTL have been shown to contribute to neurologic disease in certain viral illnesses, we examined the cerebrospinal fluid of HIV-1-infected persons with various stages of AIDS dementia complex for the presence of HIV-1-specific CTL. In five of six subjects studied, HIV-1-specific CTL were identified in the cerebrospinal fluid. These CTL were directed at epitopes within the gag, reverse transcriptase, envelope, and nef proteins and restricted by HLA class I Ag. In four of these subjects, virus-specific CTL were detected in higher numbers in the cerebrospinal fluid compared to the peripheral blood, suggesting a specific recruitment to or local induction within the nervous system. These studies demonstrate the presence of a vigorous and broadly directed CTL response to HIV-1 in the central nervous system of infected persons with AIDS dementia complex, and provide immunologic evidence of localized intrathecal infection. Although HIV-1-specific CTL may serve to inhibit viral replication in the central nervous system, the presence of a persistent CTL response in the central nervous system may also contribute to the neurologic disorders characteristic of HIV-1 infection.
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PMID:Detection of a vigorous HIV-1-specific cytotoxic T lymphocyte response in cerebrospinal fluid from infected persons with AIDS dementia complex. 138 38

To identify HIV peptides containing HLA class I binding regions, different studies have been performed. These include the detection of interactions between HIV peptides and purified HLA molecules in solid-phase assays, the measurement of HLA molecule assembly in the presence of peptide added to cell lysates, and the detection of inhibition of CTL-mediated cytolysis by competition between peptides on target cells. To date, the HIV epitopes recognized by anti-HIV CTL are from the Env, Gag, Nef, and Pol proteins and they are identified using synthetic peptides of 12 to 20 amino acids. The search for a correlation between known HIV CTL epitopes and the results of HLA/peptide interaction assays reveals that: (1) most of the peptides that are positive in the assembly assay contain a HLA-A2 peptide motif but the correlation between these positive peptides and the CTL epitopes is not obvious; (2) a high proportion of HIV epitopes are included in the peptides positive in solid-phase binding and in inhibition of cytolysis assays, although these tests do not allow us to predict HLA restriction; (3) the HLA-A2 peptide motif is not systematically included in HLA-A2-restricted CTL epitopes, this observation raising the possibility that other sequences are involved in HLA binding.
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PMID:HLA class I binding regions of HIV-1 proteins. 138 46

Review of the relationship between the degree of immunosuppression and malignancy in patients on immunosuppressive drugs or immunosuppressed by HIV infection, postoperative blood transfusion or pregnancy provides the most convincing evidence of the importance of intact T cell immunity in resistance to cancer. Defective HLA class I and II antigen expression on tumours arising in non-immunosuppressed individuals and correlation of these changes with increased malignancy and diminished TIL provide the most convincing evidence that one factor necessary to ensure survival of most spontaneous tumours is mutation that enables tumour cells to escape rejection by cytotoxic T cells. These changes are less frequent in tumours in immunosuppressed patients, and preliminary data suggest that use of cytokine therapy is more successful in these tumours and the one in five spontaneous tumours demonstrating normal expression of HLA antigens and high levels of T cell infiltration. These observations suggest that future use of this therapy should be focused on these cases. All modalities of cancer therapy except hormone therapy (ie surgery, radiotherapy and chemotherapy) suppress immune responses. Defects of HLA antigen expression are less marked in early cancer. Combinations of immunotherapy with conventional treatment at presentation, including hormone therapy in view of data demonstrating regeneration of the thymus after castration, needs further investigation. Preliminary results from randomized trials involving nearly 300 individuals accidentally exposed to carcinogens demonstrated nearly 60% reduction of incidence of malignancy at 5 years in the arm receiving non-specific immunotherapy. If confirmed, such an approach might be more cost-effective as an approach for cancer prevention than organ specific cancer screening or vaccination against cancer associated viruses such as hepatitis B or papillomaviruses.
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PMID:T cell immune response to cancer in humans and its relevance for immunodiagnosis and therapy. 142 23

The first trial of an anti-HIV immunization, using a recombinant vaccinia virus expressing gp160 (rV) for priming and paraformaldehyde-fixed rV-infected PBLs and soluble gp 160 for boosting, clearly showed an in vitro HIV-protective immune reaction. This result led us to carry out an additional 2 year Phase I clinical trial in 25 HIV-seronegative volunteers, using HIV gp 160 antigens for immunization in four different protocols. The 2 year trial showed (a) the safety of the preparations, (b) a transient humoral immunity following each boost, and (c) a long-lasting memory T-cell response. Memory cytotoxic T-lymphocytes (CTLs) induced by gp 160 antigen with or without vaccinia vector lysed HLA class I restricted target cells expressing HIV-1 env antigens. These results are consistent with CTLs being an effective component of an AIDS vaccine to control cell-to-cell viral replication, dissemination in the organism, and subsequent evolution toward AIDS.
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PMID:A 2-year follow-up of an anti-HIV immune reaction in HIV-1 gp160-immunized healthy seronegative humans: evidence for persistent cell-mediated immunity. 158 88

Burkitt's lymphoma (BL) is a highly malignant B cell tumor characterized by three types of chromosomal translocation which constitutively activate the c-myc oncogene by juxtaposing it to Ig coding sequences. Epstein-Barr virus (EBV) infection, hyperendemic malaria and HIV-caused immunosuppression are thought to contribute to the pathogenesis of the tumor. Cell lines derived from EBV carrying and EBV negative BLs often show altered MHC class I antigen expression. The defects include a lower expression of all HLA class I antigens compared to EBV transformed normal B-blasts, and selective down-regulation of certain HLA-A and HLA-C alleles. As a consequence BL cells are often resistant to cytotoxic T lymphocyte (CTL) mediated destruction. Alleles selective down-regulations are found only in cell lines that maintain the tumor cell phenotype while shift towards a more activated 'B-blast like' phenotype is accompanied by HLA class I up-regulation. A similar pattern of HLA class I expression can be found in a subpopulation of germinal center B cells which express a 'BL like' phenotype. Our findings suggest that the HLA class I expression of BL cells reflects the characteristics of the normal B cell precursor and is probably not the result of immune selection.
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PMID:Cell phenotype dependent expression of MHC class I antigens in Burkitt's lymphoma cell lines. 165 15

In order to identify the target epitopes recognized by specific CTL in the NEF protein of HIV-1, 33 peptides derived from the HIV-BRU sequence were tested with NEF-specific CTL generated from HIV-seropositive donors. Six different epitopes were identified and several points were remarkable: 1) They were all located in two regions of the central part of the NEF protein corresponding to residues 73 to 94 and 113 to 147, respectively. 2) The CTL issued from a single donor could recognize several peptides of the NEF protein. 3) Some of these peptides could be recognized in association with at least two or three different HLA class I molecules. 4) Two different overlapping epitopes were present in a relatively short sequence of 15 amino acids. These results suggest that multiple epitopes corresponding to different HLA restrictions could coexist in a relatively small region of the NEF protein. The implications of these results in vaccine strategies using synthetic peptides bearing CTL epitopes are discussed.
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PMID:Six epitopes reacting with human cytotoxic CD8+ T cells in the central region of the HIV-1 NEF protein. 170 97

The physical association of HLA class I or H-2 molecules with 36 HIV-1 Nef synthetic peptides was studied using a direct peptide binding assay (PBA) in solid phase. To assess the functional significance of the PBA results, the Nef peptides were also tested for their ability to inhibit the lytic activity of human or murine CTL. The PBA results showed that seven partly overlapping regions of the Nef protein contained MHC binding peptides (4-18, 46-67, 73-94, 100-128, 126-155, 182-198, and 192-206). Five of these seven regions included all the already described epitopes recognized by CD8+ human CTL. The two other regions, 4-18 and 46-67, are not yet described as antigenic for human CD8+ cells but they are located in the N-terminal part of Nef that was previously described as being stimulator for rat or chimpanzee CD4+ cells. Altogether, it can be concluded that 1) In virtually 100% of the cases, the PBA is capable to detect known antigenic peptides recognized by CTL. 2) The PBA and the functional inhibition assay provide similar results, supporting the functional significance of PBA results. 3) The PBA is easy to handle on a large scale, using multiple peptide and several MHC molecules, so that it can be used as a routine method for prevision of possibly epitopic sequences. 4) Systematic studies of peptides issued from the whole sequence of a given protein allow to map polyepitopic areas that are probably the most interesting parts of proteins for a vaccine purpose.
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PMID:HLA-binding regions of HIV-1 proteins. I. Detection of seven HLA binding regions in the HIV-1 Nef protein. 171 11

To detect HLA-binding peptides in 10 HIV-1 proteins (Rev, Tat, Vif, Vpr, Vpu, Gag p18, Gag p24, Gag p15, Env gp120 and Env gp41), the peptide binding assay (PBA) has been performed using three HLA class I molecules. Correlations have been searched between the PBA results and the peptide competitor activity in a functional test using HLA-A2-restricted CTL and target cells. A correlation between the data found in the PBA and well-defined CTL epitopes could be attempted only for the three Gag proteins. For these proteins, our results are in agreement with the known existence of epitopes reacting with human CD8+ CTL, with some exceptions. Together with the results reported with a panel of Nef peptides, these experiments showed that at least 18/20 of the already reported CTL epitopes from HIV-1 Gag, Nef, and Env proteins could be detected by the PBA, most (17/18) corresponding to strong reactivities. Perhaps more important, the regions of HIV-1 Gag p24 or Nef proteins that contain multiple associated CTL epitopes, with different HLA restrictions, were clearly identified by the reactivities in the PBA of several overlapping peptides and the major practical interest of the PBA might be the detection of such polyepitopic regions. Prediction are proposed in this report for 10 proteins, including several proteins for which CTL epitopes remain presently unknown.
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PMID:HLA-binding regions of HIV-1 proteins. II. A systematic study of viral proteins. 171 12

CTL directed at the highly conserved HIV-1 gag protein have been described in HIV-1 seropositive persons and may be an important host defense against this retrovirus. Presently only limited data are available regarding the specific epitopes recognized by these CTL. In this study, we have performed a detailed examination of the gag-specific CTL response in three HIV-1 seropositive subjects, using both unstimulated PBMC and cloned CTL. Lysis of gag-expressing targets was found to be mediated by CD3+CD8+ lymphocytes and restricted by class I Ag. Multiple class I Ag were found to restrict gag epitopes in each subject studied, with as many as three of these Ag involved in presenting gag CTL epitopes in a single subject. The majority of gag-specific CTL activity was found to be directed against epitopes in the p24 subunit of the gag protein, with at least seven different HLA class I-restricted CTL p24 epitopes identified in these three subjects. Less CTL activity was directed against p17 subunit of gag and two CTL epitopes were identified in this protein. Although as many as four different epitopes in gag were recognized using CTL from a single subject, none of the epitopes was recognized by CTL from more than one subject. Analysis of gag epitope recognition using cloned CTL demonstrated heterogeneity and specificity not appreciated using unstimulated PBMC. The identification of multiple relatively conserved epitopes in the HIV-1 gag protein and the heterogeneity of CTL responses to this protein may have important implications for vaccine development and our understanding of AIDS pathogenesis.
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PMID:HIV-1 gag-specific cytotoxic T lymphocytes recognize multiple highly conserved epitopes. Fine specificity of the gag-specific response defined by using unstimulated peripheral blood mononuclear cells and cloned effector cells. 171 61

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


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