Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peptide-based vaccines that directly target T cell or B cell epitopes may have significant advantages over conventional vaccines. Further, synthetic chimeric peptides that combine strong T cell epitopes with poorly immunogenic, but immunodominant, B cell epitopes or strain-conserved B cell epitopes may be useful in eliciting antibody to such important regions. Here we characterize a human T cell epitope analyzed in 54 individuals immunized with a hepatitis B virus surface Ag vaccine. Primary cultures from a total of 59 immunized donors were assessed for their ability to respond to hepatitis B virus surface Ag and peptides, and five were non-responders (8.5%). T cell lines were established from the remaining 54 responders. Of the responders, it was found that the peptide representing amino acids 19 through 33 (19-33) elicited significant proliferation in lines derived from 50 donors. This "universal" T cell epitope, which was recognized in donors of many different HLA-DR and -DQ haplotypes, was then used to construct a chimeric peptide containing 19-33 and the third V region loop structure (V3 loop) of HIV-1 envelope gp 120, in an attempt to augment the immune response to the V3 loop peptide. The V3 loop is the region to which significant neutralizing antibody is directed. Thus, a strong immune response to a synthetic peptide that contains the strain-conserved V3 loop region could have significant therapeutic implications. The V3 loop/19-33 peptide was then used to prime mice, to determine whether V3 loop-specific antibody could be induced. The peptide elicited potent 19-33-specific proliferation in T cells isolated from draining lymph nodes, and in six of six mice anti-V3 loop antibody was elicited. Further, V3 loop/19-33-primed animals made significant levels of antibody that bound rgp120. These data suggest that, when a major T cell epitope is synthesized in tandem with the V3 loop, a significant immune response against the loop can be elicited. Thus, given the finding that neutralizing antibody may play a role in the control and/or prevention of HIV infection, an HIV vaccine composed of a T cell epitope-containing peptide may prove effective. In addition, this type of approach can be generalized to the design of peptide-based vaccines.
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PMID:A universal T cell epitope-containing peptide from hepatitis B surface antigen can enhance antibody specific for HIV gp120. 137 46

The distribution of the thrombospondin-receptor was studied in 26 cases of inflammatory hepatitis B virus (HBV) related liver disease and twelve non-inflammatory controls using monoclonal antibody (mcab) OKM5. OKM5 reacted in all cases with sinusoidal lining cells, portal vessel endothelium, and scattered mononuclear inflammatory cells. In 16 of the 26 cases with inflammation, one or more clusters of OKM5 positive (OKM5+) hepatocytes were found in areas of periportal or intralobular inflammation, whereas the remaining ten cases did not show hepatocellular OKM5 reactivity. In all but one case, OKM5+ liver cells coexpressed HLA-DR-antigens, and in twelve cases cytotoxic/suppressor T-cells were enriched in the OKM5+/HLA-DR+ liver cell clusters, suggesting induction of OKM5 positivity by lymphokines released by nearby T-cells. In view of its role in cytoadherence, it is suggested that OKM5 expression by hepatocytes serves in the entrapment and retention of inflammatory cells thereby facilitating their activation. Furthermore, OKM5+/HLA-DR+ hepatocytes might trigger an autologous mixed lymphocyte reaction (AMLR), resulting in down-modulation of ongoing hepatic inflammatory responses.
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PMID:Adhesive molecules in liver disease. Immunohistochemical distribution of thrombospondin receptors in chronic HBV infection. 169 75

Although hepatitis B (HB) virus-associated pre-S2 Ag may be important in facilitating the uptake of virions into hepatocytes, it is not clear whether the anti-pre-S2 antibody plays a substantial role in the protection from infection in man. The mechanisms underlying the nonresponsiveness to the HB vaccine are not clear. To evaluate the immunological background in nonresponders to pre-S2 Ag, HLA-DR/DQ antigens and the production of antibodies to pre-S2 Ag and HBs Ag were estimated in vitro on medical healthy personnel. Ninety-one males and 213 females were vaccinated with pre-S2 Ag positive plasma-derived HB vaccine three times. Four months after the third vaccination, blood was withdrawn for pre-S2 antibody test by ELISA. Antibodies to pre-S2 Ag were found in 19.8% of the individuals. Nonresponders were observed at a higher frequency in males than females, and they were seen more frequently in the elderly than young individuals. In aged subjects, aging seemed to be the major factor in their unresponsiveness. A high frequency of HLA-DR4.DRw53.DQw3 haplotype was observed in the subjects with nonresponsiveness against pre-S2 Ag. In order to induce the secretion of anti-HBs antibody, we investigated the effect of simultaneous administration of HBs Ag and immunoglobulin containing anti-HBs antibody on the antibody responses in vitro. In vitro stimulation of mononuclear cells from 10 individuals who failed to respond or responded poorly to HB vaccine induced a significant amount of anti-HBs antibody in 5 cases, whereas stimulation with HBs Ag alone failed to induce the antibody secretion in most cases.
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PMID:[Antibody responses in human being to pre-S2 and related hepatitis B virus-envelope antigens in vivo and in vitro]. 182 38

Genetic control of immune response was investigated by family and population analyses in humans. It was first recognized that there are high responders and low or non responders to natural antigens in human population. Family analysis revealed that low responsiveness to streptococcal cell wall antigen (SCW) was inherited as an HLA-linked dominant trait. CD8+ suppressor T cells existed in low responders and depletion of the CD8+ T cells from low responders could restore the strong immune response to SCW. Therefore the gene controlling the low response to SCW was designated as an immune suppression gene for SCW. Immune suppression gene for SCW was in strong linkage disequilibrium with particular alleles of HLA-DQ locus. The association between HLA-DQ alleles and low responsiveness mediated by CD8+ suppressor T cell was also observed for schistosomal antigen, Mycobacterium leprae antigen, tetanus toxoid, cryptomeria pollen antigen and hepatitis B virus surface antigen suggesting that low responsiveness to those antigens was also controlled by immune suppression genes. Anti-HLA-DR monoclonal antibodies inhibited the immune response to those antigens of high responders in vitro, but anti-HLA-DQ monoclonal antibodies did not. On the other hand, anti-HLA-DQ monoclonal antibodies restored the immune response in low responders. Therefore, it is suggested that HLA-DR upregulates immune response and that HLA-DQ downregulates it and that HLA-DQ is epistatic to HLA-DR in the regulation of immune response in humans. Furthermore, direct evidence for the differential in immune regulation between HLA-DR and DQ was obtained by analyzing the SCW specific T cell lines from low responders. SCW specific and HLA-DQ restricted CD4+ T cell lines could activate CD8+ suppressor T cells which in turn downregulate SCW specific CD4+ T cells whereas SCW specific and HLA-DR restricted CD4+ T cell lines could not activate CD8+ suppressor T cells. All these observation clearly demonstrated that the HLA-linked immune suppression genes exist in humans to control low response to natural antigens.
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PMID:HLA-linked immune suppression genes. 214 11

Hepatocellular injury during hepatitis B virus (HBV) infection has been postulated to result from a human leukocyte antigen (HLA)-restricted T-lymphocyte host immune response against HBV antigens. Although HLA expression is enhanced in the presence of hepatic inflammation, whether HBV itself can induce HLA expression on infected hepatocytes is unknown. In this study, we demonstrate the induction of HLA-DR expression on human hepatoma cell lines transfected with HBV DNA sequences. The HBV X gene alone was capable of inducing HLA-DR expression. This induction correlated with elevated HLA-DR RNA, and this resulted directly from transcriptional trans-activation of the HLA-DR gene by the HBV X protein. These studies suggest that the HBV X protein can regulate the expression of HLA-DR and thus raise the possibility of participation by the X gene in the immunopathogenesis of HBV infection.
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PMID:Trans-activation of HLA-DR gene by hepatitis B virus X gene product. 216 20

Interferon-alpha (IFN-alpha) has been reported to be beneficial in the treatment of chronic active hepatitis occurring as a result of hepatitis B virus (HBV) infection. Treatment with IFN-alpha has been proposed as a means of reducing the high rate of allograft infection in clinical liver transplantation in patients transplanted for HBV-related chronic active hepatitis and cirrhosis who are positive for hepatitis B surface antigen (HBsAg). We obtained resected whole livers from two groups of patients who received liver transplants. Group A consisted of 11 patients who were HBsAg+ but were not treated with IFN-alpha, and group B consisted of 10 patients who were also HBsAg+ but received IFN-alpha therapy for 29.4 +/- 5.6 days prior to orthotopic liver transplantation. No differences between the two groups existed in terms of a variety of demographic and clinical characteristics. The liver tissue was stained with monoclonal antibodies to cell surface antigens unique to different mononuclear cell populations by the avidin-biotin-immunoperoxidase technique to determine the effect of IFN-alpha on the lymphocyte subsets as well as HLA antigen expression on liver-infiltrating mononuclear cells. The number of HLA-DR+ lymphocytes in the liver was significantly increased (P less than 0.005) within the portal areas in group B compared with that found in group A (84 +/- 14 versus 33 +/- 5 per one high-power field). Moreover, the intensity of the HLA-DR antigen expression on lymphocytes in the portal areas (P less than 0.02) and in the hepatic lobule (P less than 0.05) was greater in group B than in group A. The number of natural killer (NK) cells was increased in the portal areas (P less than 0.05) of group B compared with group A. These alterations in the lymphocyte and NK cell populations present in the liver in response to IFN-alpha therapy presumably reflect an IFN-alpha-induced enhancement of the immune response to virus-infected cells.
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PMID:The effect of recombinant interferon-alpha on lymphocyte subpopulations and HLA-DR expression on liver tissue of HBV-positive individuals. 224 14

Major histocompatibility complex antigens are critical to an animal's immune response. In most animals, the extreme polymorphism of MHC molecules complicates studies of the role of this complex in the immune response. In mice, however, MHC haplotype-homozygous inbred strains have been developed which are invaluable in the study of the immune system and the search for immune response genes. The human MHC bears many similarities to its murine equivalent with regard to antigen structure and polymorphism; furthermore, a number of combinations of specific MHC alleles between HLA-B and HLA-DR/DQ (extended haplotypes) are found in people more commonly than predicted by individual allele frequencies. Over 30 percent of Caucasian haplotypes are extended haplotypes, and over 55 percent of individuals have at least one extended haplotype. Examples of the same extended haplotype, even in unrelated individuals, should either all have or lack any gene within the MHC region. The value of considering extended haplotypes in searching for associations between the MHC and diseases, or immune response, is shown in three examples: congenital adrenal hyperplasia, hepatitis B immunization, and transfusion-associated graft-versus-host disease.
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PMID:The major histocompatibility complex: the value of extended haplotypes in the analysis of associated immune diseases and disorders. 229 6

HLA antigens, hepatitis B virus (HBV)-associated antigens and lymphocyte subsets in liver tissue from 35 patients with HBs antigenemia were studied using an immunoperoxidase double staining method and immunoelectron microscopy in order to clarify the immune mechanism of hepatocyte lysis in type B hepatitis. Immune light and electron microscopy using monoclonal antibodies to lymphocyte subsets revealed that infiltrating lymphocytes in the areas of piecemeal necrosis and focal necrosis were predominantly CD8-positive, showing direct contact with hepatocytes. In contrast, CD4(+) cells were infrequently observed in necrotizing inflammatory lesions. HLA-A,B,C antigens were mainly found on hepatocytes in areas of piecemeal necrosis and focal necrosis, in association with CD8(+) lymphocyte infiltration. HLA-DR antigens were demonstrated on a few hepatocytes in the same lesions. In cases of CAH with serum HBeAg positive, HLA-A,B,C, antigens and HBV antigens simultaneously demonstrated on the same hepatocytes. Especially, hepatocytes expressing both HLA-A,B,C antigen and HBsAg on the plasma membrane showed direct contact with CD8(+)lymphocytes. This finding fulfilled the morphological requirements for HBsAg as a target antigen. On the other hand, HBcAg was hardly demonstrated in the liver cell membrane but was demonstrated mainly in the cytoplasm. Compared with the nuclear localization of HBcAg in cases of NSR, cytoplasmic localization of this antigen may be associated with membranous expression of new antigens induced by HBV infection.
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PMID:Immunohistochemical investigation of hepatitis B virus associated antigens, HLA antigens and lymphocyte subsets in type B chronic hepatitis. 240 98

By using a preparation of inactivated rabies virus, the blood mononuclear cells from five rabies vaccine recipients were stimulated in vitro in the presence of interleukin 2. T cell lines that displayed significant proliferative responses to whole rabies virus and to preparations of rabies glycoprotein and nucleocapsid were obtained from all the individuals. Other antigens, such as diphtheria and tetanus toxoids, influenza A virus, hepatitis B surface antigen, and serum albumin, failed to induce the proliferation of the T cell lines. One of these rabies-specific T cell lines was found to proliferate in response to rabies antigens only when the antigen-presenting cells expressed homologous HLA-DR antigens. The use of mouse monoclonal antibodies specific for human T cell surface markers revealed that most of the cells of these rabies-reactive lines were of the helper/inducer class of T lymphocytes. Stimulation of the T cell lines with the rabies antigens induced the production of interferon-gamma, a lymphokine with potent antiviral activity. Several T cell clones were isolated from two of these cell lines, and most of them appeared to be specific for the antigenic components of the viral nucleocapsid. Two T cell clones specific for the rabies glycoprotein were also isolated from one of these lymphocyte interleukin 2-dependent lines. Further in vitro studies with rabies-specific T cells could help us to understand in more depth the role of regulatory T cells in the human immune response to rabies virus.
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PMID:Isolation and characterization of human T cell lines and clones reactive to rabies virus: antigen specificity and production of interferon-gamma. 241 20

Alpha-interferon (IFN-alpha) has been shown to be beneficial in the treatment of chronic active hepatitis occurring as a consequence of hepatitis B virus (HBV) infection. Therefore, it has been used to reduce the high rate of allograft infection in clinical liver transplantation of HBV-positive individuals. This study was performed to evaluate the effect of IFN-alpha on lymphocyte subsets as well as the HLA-DR antigen expression in liver tissue. The resected livers obtained from two groups of patients who received liver transplants between 1983 and 1987 at the University of Pittsburgh were examined: group A consisted of 11 patients who were not treated (controls), and group B consisted of 10 patients (experimental group) who were treated with IFN-alpha for 29.4 +/- 5.6 days prior to transplantation. No differences between the two groups existed in terms of a variety of demographic and clinical characteristics. Both groups had cirrhosis as a result of chronic HBV infection. Monoclonal antibodies to cell-surface antigens unique to different lymphocyte populations and the HLA-DR antigens were used in conjunction with the avidin-biotin-immunoperoxidase technique to identify cells in tissue sections. The number of HLA-DR-positive lymphocytes in the liver was increased (P less than 0.005) within the portal areas in rIFN-alpha-treated group as compared to that seen in the untreated group (84.4 +/- 13.6/HPF vs 33.3 +/- 4.8/HPF). Moreover, the intensity of the HLA-DR antigen expression in the portal areas (P less than 0.02) and in the hepatic lobule (P less than 0.05) was greater in the treated group than in untreated group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alpha-interferon. Its effect upon lymphocyte subpopulations and HLA-DR expression within the liver. 253 Oct 67


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