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Results for “Histocompatibility Antigens Class II”

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At least 19 recordsLinked to original sources

PubMed1992

Stromal macrophages of the choroid plexus situated at an interface between the brain and peripheral immune system constitutively express major histocompatibility class II antigens.

Using immunocytochemistry we have shown that there is a population of macrophages within the stroma of the choroid plexus of rats and mice which expresses high levels of major histocompatibility complex Class II antigens. In whole mount preparations of the choroid plexus, the morphology and regular distribution of these cells is similar to the Langerhans cells of the skin. These cells reside at an important interface between the central nervous system and the peripheral immune system and their possible role in immune-mediated diseases of the central nervous system is discussed.

Animals↗

PubMed1992

Stress-induced alterations in interferon production and class II histocompatibility antigen expression.

Mild electric foot-shock has been shown to be a stressor that can alter immune responses. Male Lewis rats were exposed to one session of 16 5.0-s 1.6-mA foot-shocks. Production of interferon-gamma by splenocytes in response to concanavalin-A was decreased in spleens from the shocked rats compared to control spleens. Spleen cells from rats treated with nadolol, a peripherally acting beta-adrenergic receptor antagonist, and then shocked, showed dose-dependent attenuation of the suppression of interferon-gamma production. This suggests that catecholamines mediate shock-induced suppression of interferon-gamma production. The percentage of splenic mononuclear cells expressing class II histocompatibility (Ia) antigens on their surfaces from spleens of shocked rats was determined by flow cytometry. Significantly decreased class II positive mononuclear cells were present in the spleens of shocked rats in comparison to the spleens of control rats. This may reflect an alteration of cell trafficking or decreased production of class II antigens.

Animals↗

PubMed1992

Cyclic variation of major histocompatibility complex class II antigen expression in the human fallopian tube epithelium.

OBJECTIVE: To systematically investigate the expression of major histocompatibility complex (MHC) class II antigens (human leukocyte antigens, HLA-DR, -DP, and -DQ) on columnar epithelium in the fallopian tube during the menstrual cycle. STUDY DESIGN: Biopsies were collected from the fallopian tube during laparotomy sterilization and immunoperoxidase staining was performed. SETTINGS: Departments of Gynecology and Obstetrics and Clinical Immunology and Transfusion Medicine, Uppsala University, Uppsala, Sweden. PATIENTS: Twenty healthy fertile women undergoing sterilization at different times of the menstrual cycle. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The staining of the columnar epithelium was judged on a 4-graded scale according to the distribution of class II antigens. RESULTS: A widespread preovulatory HLA-DR expression was observed almost completely lining the columnar epithelial cells including the luminal surface, whereas postovulatory the HLA-DR expression was withdrawn from the surface. The HLA-DP and -DQ antigens varied in a similar way, although not as pronounced. CONCLUSIONS: The MHC class II antigen variation in the fallopian tube epithelium seen in this study may indicate a hormonal regulation that could reflect variable need for local immunocompetence during the menstrual cycle: a preovulatory need for immunoreactivity against invading microbes and postovulatory an optimal survival of the foreign preimplantation embryo.

Epithelium↗

PubMed2004

Bovine leukocyte antigen major histocompatibility complex class II DRB32703 and DRB31501 alleles are associated with variation in levels of protection against Theileria parva challenge following immunization with the sporozoite p67 antigen.

Initial laboratory trials of an experimental subunit vaccine against Theileria parva based on the 67-kDa major sporozoite surface antigen revealed a range of responses to challenge. We have analyzed convergence in seven sets of monozygotic twins which suggests that genetic factors may have an influence in determining the degree of protection provided by p67 immunization. In addition, we have examined whether allelic diversity at major histocompatibility complex class II loci influences protection. Analysis of bovine leukocyte antigen DRB3 diversity in 201 animals identified significant associations with vaccine success (DRB3*2703; P = 0.027) and vaccine failure (DRB3*1501; P = 0.013). Furthermore, DRB3*2703 was associated with the likelihood of immunized animals showing little to no clinical signs of disease following challenge. We discuss the acquired and innate immune mechanisms that may be behind the associations described here.

Alleles↗

PubMed1992

Typing for major histocompatibility complex class II antigens in thyroid tissue blocks: association of Hashimoto's thyroiditis with HLA-DQA0301 and DQB0201 alleles.

This study was undertaken 1) to find out whether we can type major histocompatibility class II antigens from the paraffin-embedded series of thyroid tissue, and 2) to investigate whether HLA-DQ genes are involved in conferring a risk of Hashimoto's thyroiditis. To this end we used the polymerase chain reaction to amplify DNA from paraffin-embedded thyroid tissue blocks of histologically proven Hashimoto's disease. We used 46 specimens for HLA-DQA and 32 for DQB typing. The alleles were identified by sequence-specific oligonucleotide hybridizations. Fifty controls from the same geographic region were also typed using peripheral leukocyte DNA. HLA-DQA0301 (in linkage disequilibrium with DR4) was significantly increased (58.7% vs. 32% in controls; chi 2 = 6.73; P less than 0.01) in patients compared to controls. DQB0201 (in linkage disequilibrium with DR3) was also increased in the patient group (66% vs. 36% in controls; chi 2 = 6.63; P less than 0.01). Although DQA0301/DQB0201 heterozygotes (18.8%) were increased in patients compared to controls (6%), the difference was not significant. However, 81% of the patients (26 of 32) were DQA0301 and/or DQB0201 positive compared to 48% of controls (chi 2 5.98; P less than 0.05). We conclude that it is feasible to type HLA antigens from tissue blocks and that susceptibility to Hashimoto's disease is probably mediated through two pathways: DQA0301/DR4 and DQB0201/DR3.

Alleles↗

PubMed1992

Regional variation in ontogeny of class II antigens in enterocytes of mouse small intestine.

The ontogeny of major histocompatibility class II antigens in small intestine enterocytes of postnatal C3H/He mice was investigated. Cryosections of duodenal, jejunal, and ileal segments from 7-, 14-, 16-, 20-, 21-, 23-, 25-, 27-, 28-day-old and 7-week-old mice were stained for the class II antigens with MRC OX6 monoclonal antibodies by peroxidase-antiperoxidase labelling. In adults, the duodenum exhibited least expression of class II antigens that increased progressively towards the ileum. The expression in the villous epithelium was first seen in the duodenum and jejunum 21 days after birth but the ileal enterocytes did not exhibit any class II antigens. The earliest appearance (21 days postnatal) of class II antigens in the enterocytes coincides with the age of weaning which suggests that immunologic stimulation by ingested antigens after weaning may influence expression of these antigens. At day 28 after birth, the duodenum and jejunum expressed levels comparable to those in the adults. The first expression of the antigens seen in the ileum was at day 28 postpartum. Crypt epithelium of the three regions of the small intestine showed expression similar to that of corresponding regional villous enterocytes. We conclude that there is an age-dependent regional variation in the expression of class II antigens in enterocytes, and the expression increases with age. The variation in expression of the class II antigens in enterocytes of postnatal mice is attributed to the developmental status of the tissue. The nature of postnatal expression of the antigens is important since an early appearance of these antigens may have implications in autoimmunity.

Aging↗

PubMed1992

Ectopic class II major histocompatibility antigens in Hirschsprung's disease and neuronal intestinal dysplasia.

Although the etiology of Hirschsprung's disease and neuronal intestinal dysplasia remains obscure, both have histological abnormalities involving ganglion cells and neuronal elements. Searching for a common pathway that may inhibit normal maturation of neurogenic precursors, we examined the possible role of an immune mechanism in the maldevelopment of the enteric neural network. Six patients with Hirschsprung's disease were studied by comparing biopsy specimens from diseased colon with ones taken from proximal ganglionic colon in the same patients. These were similarly compared with colonic biopsy specimens from patients studied with chronic constipation or bowel removed at the time of operation for other disorders. Biopsies were taken from four other patients with neuronal intestinal dysplasia. Each was examined by hematoxylin & eosin staining, acetylcholinesterase histochemistry, and immunohistochemistry of major histocompatibility complex (MHC) class I and class II antigens. All rectal samples from Hirschsprung's disease patients exhibited elevated acetylcholinesterase histochemistry and absent ganglia to confirm the diagnosis. These findings were correlated with marked elevation of class II MHC in the aganglionic area, whereas the proximal normal ganglionic segments showed no elevation. Rectal biopsy specimens from patients with chronic constipation exhibited no such elevation. A similar elevation of class II MHC was detected in the mucosa and submucosa of all four patients with the rare neuronal intestinal dysplasia disorder whose diagnosis was confirmed by giant ganglia in Auerbach's plexuses, aberrant Meissner's ganglia in the lamina propria mucosa, and giant neurofibrils in the mucosa and submucosa. The correlation of elevated class II MHC in these two neuronal dysfunction disorders may indicate an underlying autoimmune mechanism as is seen in thyroiditis and insulin dependent diabetes mellitus.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗

PubMed1992

Relative abilities of distinct isotypes of human major histocompatibility complex class II molecules to bind streptococcal pyrogenic exotoxin types A and B.

The relative ability of distinct isotypes of human leukocyte antigen class II molecules to bind streptococcal pyrogenic exotoxins A and B (SPE A and SPE B, respectively) was investigated by a direct-binding assay with 125I-labeled toxin for SPE A and by a functional assay system measuring the accessory cell activity of human leukocyte antigen class II transfectants in toxin-induced T-cell activation for SPE A and SPE B. SPE A binding was observed in L cells transfected with DQw1 genes. By contrast, it was not detected in L cells transfected with DR2, DR4, DPw4 or DP(Cp63) genes. All the transfectants supported SPE-induced interleukin-2 production by human T cells except the DP transfectants for SPE B. Levels of accessory cell activity were low in the DP transfectants induced by stimulation with SPE A and in the DR and DP transfectants induced by SPE B. The results indicate that SPE A and SPE B bind well to DQ molecules, less well to DR molecules, and very weakly to DP molecules.

Animals↗

PubMed1992

Biochemical evidence for the rapid assembly and disassembly of processed antigen-major histocompatibility complex class II complexes in acidic vesicles of B cells.

Helper T cell recognition of antigen requires that it be processed within antigen-presenting cells (APC) to peptide fragments that subsequently bind to major histocompatibility complex (MHC) class II molecules and are displayed on the APC surface. Heretofore, processed antigen-MHC class II complexes have been detected by functional assays, measuring the activation of specific T cells. We now report direct, biochemical evidence for the assembly of processed antigen-MHC class II complexes within splenic B cells as APC. The I-Ek MHC class II molecules were immunoprecipitated from B cells that had processed the model protein antigen cytochrome c radiolabeled across its entire length by reductive methylation of lysine residues and covalently coupled to Ig-specific antibodies, allowing internalization after binding to surface Ig. Our previous studies showed that I-Ek immunoaffinity purified from B cells that had processed cytochrome c contains functional processed antigen--MHC class II complexes and that approximately 0.2% of the I-Ek molecules are specifically associated with one of two predominant processed antigenic fragments. Here we show that these complexes are rapidly assembled, within 30-60 min after antigen binding to surface Ig on splenic B cells. Maximal numbers of complexes are assembled by 2 h in a process that is sensitive to acidic vesicle inhibitors but not to inhibitors of protein synthesis. The processed antigen-I-Ek complexes have a relatively short half-life of 2-4 h and are disassembled or degraded within 8 h after antigen is first internalized. The disassembly or degradation of the processed antigen-I-Ek complexes requires acidic vesicle function, and in the presence of an acidic vesicle inhibitor the complexes are long lived. Thus, using a biochemical assay to monitor processed antigen-I-Ek complexes, we find that, in B cells, processed antigen is relatively rapidly associated in acidic vesicles with preexisting MHC class II molecules, and the complexes are disassembled 4-6 h later in processes that also require acid vesicle function.

Acids↗

PubMed1992

Major histocompatibility complex-linked transport proteins and antigen processing.

The major histocompatibility complexes of mice, rats and humans each contain a pair of related genes, Tap-1 and Tap-2, that encode members of a large superfamily of proteins having similar structure and function. The TAP-1 (previously called HAM1 in the mouse) and TAP-2 (HAM2) proteins each contain 6-8 predicted membrane-spanning alpha helices, and a cytoplasmic domain containing a putative ATP-binding site. Recent evidence suggests that a functional TAP-1/TAP-2 heterodimer is required for efficient presentation of antigens to CD8+ cytotoxic T cells. This heterodimer resides in the membrane of the endoplasmic reticulum (ER), and probably functions to transport peptides (produced in the cytoplasm) into the ER lumen for binding to MHC class I molecules.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1992

Rejection of murine congenic bile ducts: a model for immune-mediated bile duct disease.

Immune-mediated injury of prenatal and postnatal extrahepatic bile duct epithelium has been poorly characterized. In a transplantation model of bile duct allografts, segments of the common bile duct from fetal day 18, postnatal day 7 and day 21, and adult (greater than 6-weeks) mice were grafted under the renal capsule of adult congenic mice. The progression of rejection injury in these bile duct allografts was then followed by histological evaluation at 1-week intervals. After 3 weeks there was a significant difference in the number of fetal congenic bile duct grafts that had maintained their luminal architecture compared with the more mature adult congenic grafts that had fibrosclerosed. The onset and progression of the rejection injury in the adult congenic bile duct grafts was associated with an induction of class I and class II histocompatibility antigen expression in the adult bile duct epithelium; the severity of this injury could be attenuated by treatment of the recipient mice with cyclosporin A. Thus, the fibrosclerosing lesion of extrahepatic ducts observed in this model of rejection injury is similar to the histopathology of neonatal biliary atresia or primary sclerosing cholangitis, and susceptibility to this injury is dependent on the age of the donor tissue. The immune nature of the injury and the ontogeny of expression of histocompatibility antigen in bile duct tissue indicate that the above factors may be important to the pathogenesis of these extrahepatic bile duct diseases. This experimental model may be used to test for novel factors that may modulate immune responses directed against extrahepatic bile duct epithelium.

Animals↗

PubMed1992

Induction of class II major histocompatibility antigens on thyroid, adult pancreatic islet, and fetal proislet allografts.

Cultured BALB/c (H-2d) thyroid, adult pancreatic islet and fetal proislet tissues can be accepted permanently in CBA/H (H-2k) recipients until rejection is triggered by the transfer of antidonor strain activated immune T cells. Class II MHC antigens are not expressed on the accepted grafts and are induced following immune cell transfer, but expression is quantitatively and qualitatively different for the different tissues. Thyroid allografts show intense class II MHC antigen expression early after immune cell transfer and before extensive tissue destruction has occurred. In contrast, adult islet and fetal proislet allografts show patchy and cytoplasmic staining usually associated with areas of tissue destruction. Gamma-interferon treatment of tissues in vitro showed that proislet tissue has a greater capacity for class II MHC antigen induction than adult islet tissue. The differences in the capacity for class II MHC induction by fetal and adult islet tissue may be important in relation to the pathogenesis of autoimmune disease.

Animals↗

PubMed1992

Cell subsets responding to purified hepatocytes and evidence of indirect recognition of hepatocyte major histocompatibility complex class I antigen. II. In vitro-generated "memory" cells to class I+ class II- hepatocytes.

Purified hepatocytes stimulate the development of L3T4-, Ly2+ allospecific cytolytic T cells from naive splenocytes after 5 days in primary mixed lymphocyte-hepatocyte culture (MLHC). Previous studies indicate that the immunogenicity of purified hepatocytes relates to the expression of MHC class I antigen. The purpose of the following experiments was to identify the cell subsets that specifically recognize hepatocyte MHC class I antigen. We employed primed lymphocyte testing (PLT) in order to test for a "second set" response. Cells from primary MLHC reverted to a functionally quiescent state when they were grown in culture for an additional 7-9 days. The cells were then tested for cytotoxicity or rechallenged with allogeneic, syngeneic, or "third party" hepatocytes and tested for proliferation. Allocytotoxicity was low on day 12 in MLHC, but the sensitized cell population demonstrated peak proliferation in response to allogeneic hepatocytes 48 hr after restimulation. When bulk PLT cells were immunodepleted, both L3T4+, Ly2- and L3T4-, Ly2+ T cell subsets demonstrated a "second set" response to allogeneic hepatocytes consistent with specific recognition of and retention of "memory" for hepatocyte MHC class I alloantigen.

Animals↗

PubMed1992

Involvement of major histocompatibility complex class II antigen in Epstein-Barr virus-mediated B cell proliferation.

Five MHC class II monoclonal antibodies costimulated proliferation of cord blood leukocytes with Epstein-Barr virus. These agonistic antibodies were of different isotypes, but all of them were either specific for or cross-reacting with HLA-DR. The other MHC class II antibodies, including three that were specific for HLA-DQ and one that was specific for HLA-DP and also those that were specific for MHC class I or leukocyte common antigen, were not costimulatory. The agonistic effect of different MHC class II antibodies was additive, such that costimulation by different antibodies combined significantly exceeded that achieved by either of these antibodies alone. Spent culture media of B cell lines also costimulated B cell proliferation with the virus. Although MHC class II antibodies augmented the effects of suboptimal concentration of the conditioned media, their combined effects did not exceed the maximum costimulation achieved by either the antibodies or the spent culture media alone. These results raised the possibility that MHC class II antigen may contain distinct functional domains involved in the regulation of B cell progression.

Antibodies, Monoclonal↗

PubMed1992

N-linked oligosaccharides of murine major histocompatibility complex class II molecule. Role in antigenic peptide binding, T cell recognition, and clonal nonresponsiveness.

To evaluate the functional role of the N-linked oligosaccharides of major histocompatibility complex (MHC) class II molecules, affinity-purified murine IAs class II molecules were deglycosylated in the presence of asparagine amidase enzyme. The deglycosylated IAs molecules were characterized by 12% SDS-polyacrylamide gel analysis under reduced and native conditions and the complete enzymatic removal of all three N-linked sugar components from the alpha/beta heterodimer was confirmed by lectin-link Western blot analysis. Like the native IAs molecules, the deglycosylated IAs molecules were fully capable of binding an antigenic peptide from myelin basic protein MBP(89-101). The kinetics of dissociation of preformed complexes of IAs.MBP(89-101) and deglycosylated IAs.MBP(89-101) were compared at 4 and at 37 degrees C. Both complexes were equally stable at 4 degrees C; however, at 37 degrees C the deglycosylated IAs.MBP(89-101) complexes showed an increased rate of dissociation as compared with the native IAs.MBP(89-101) complexes. When tested for their ability to recognize the T cell receptor on T cells, both complexes bound to cloned HS-1 T cells that recognize and respond to IAs.MBP(89-101). Finally, the complexes of deglycosylated IAs.MBP(89-101) were tested for the induction of in vitro nonresponsiveness and compared with native IAs.MBP(89-101) complexes. Both complexes were capable of inducing 95-100% nonresponsiveness in a proliferation assay. These results suggest that the N-linked oligosaccharide of MHC class II molecules may not be essential for either antigenic peptide binding or T cell recognition. In addition results obtained here provide evidence that the carbohydrate moities of MHC class II molecules may not be involved in induction of T cell clonal anergy.

Amidohydrolases↗

PubMed1992

Palmitic acid conjugation of a protein antigen enhances major histocompatibility complex class II-restricted presentation to T cells.

The effect on antigenicity of covalent attachment of lipid groups to a protein antigen was investigated. Coupling of palmitic acid to ovalbumin (OVA) enhanced major histocompatibility complex (MHC) class II-restricted presentation to most OVA-specific murine T-cell clones in vitro. The enhanced antigenicity of palmitoylated antigen was localized to the level of presentation of the synthetic peptide epitope, OVA 323-339. T-cell responses to palmitoylated antigen were more difficult to block with anti-MHC class II antibodies than responses to native antigen. However, T-cell proliferation to palmitoyl (p)-OVA and native (n)-OVA were blocked equally by anti-CD4 antibodies. Taken together, the results suggest that lipid conjugation of a protein antigen leads to the formation of a lipopeptide T-cell epitope with increased affinity of binding to MHC class II and/or T-cell receptor (TcR). These results have implications for the design of synthetic peptide vaccines.

Adjuvants, Immunologic↗

PubMed1992

CD4+ T cell-mediated killing of major histocompatibility complex class II-positive antigen-presenting cells (APC). III. CD4+ cytotoxic T cells induce apoptosis of APC.

A subset of CD4+ T cells, belonging to the T helper type 1 (Th1) cells, kills antigen-presenting cells (APC) in an antigen-specific and major histocompatibility (MHC) class II-restricted way. Evidence is presented that CD4+ cytotoxic T lymphocytes (CTL) induce apoptosis or programmed cell death within susceptible APC as witnessed by quantitative DNA fragmentation. Apoptosis is more reliable to determine cell death than the 51Cr-release assay, because some cells demonstrate resistance to CD4-mediated lysis in the 51Cr-release assay. Apoptosis becomes manifest after 2 to 4 h of incubation preceding the disintegration of the target cells which is detectable between 12 and 24 h as measured by the 51Cr-release assay. Unstimulated B cells, which are not killed, but function as APC, do not undergo apoptosis, whereas lipopolysaccharide or anti-mu-activated B cell blasts show apoptosis and are efficiently lysed. Several CD4+ Th2-type cells tested, which did not demonstrate killing of APC as measured by the 51Cr-release assay, are unable to mediate programmed cell death of appropriate APC. Actinomycin D or cycloheximide, inhibitors of transcription and translation, respectively, fail to prevent apoptosis of APC excluding the involvement of newly synthesized soluble products as mediators of killing. Pretreatment of CD4+ CTL, but not of APC with 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, a specific inhibitor of the anion transport, efficiently prevents apoptosis of APC, although the secretion of interleukins is not affected. We propose, that upon contact of the CD4+ CTL with APC, molecules of yet undefined nature are activated and released in a polar fashion at the contact site and induce the endogenous pathway of programmed cell death.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed1992

Virus infection blocks the processing and presentation of exogenous antigen with the major histocompatibility complex class II molecules.

Helper T cell recognition of antigen requires that antigen be processed and presented by class II expressing antigen-presenting cells (APC). Many antigens presented by the immune system are part of infectious organisms, for example, bacteria and viruses, which themselves may affect APC function. Here we show that infection of B cell lines as APC with viruses of two different families, namely, influenza A or vaccinia, completely block processing and presentation of an exogenous globular protein antigen pigeon cytochrome c. The block appears to be primarily within the processing pathway, as virus infection has little effect on the presentation of an antigenic peptide of pigeon cytochrome c which does not require processing. It is likely that several steps in the processing pathway are affected. Only live infectious virus, not UV-inactivated virus blocks APC function, indicating that there is no competition of viral particles with cytochrome c for the class II processing machinery. As compared to uninfected cells, virus-infected cells internalize less antigen bound to surface Ig but degrade a similar portion of that which enters the cell. Virus infection results in reduced protein synthesis in APC which may also be a factor in decreasing APC function. Significantly, we show that the processing of a high affinity evolutionary variant of cytochrome c from Drosophila melanogaster is reduced less by virus infection as compared to c. Such knowledge may guide the selection of antigenic epitopes in vaccine design.

Animals↗