PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “antigen presentation”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources

Can resting B cells present antigen to T cells?

Antigen stimulation of T lymphocytes can occur only in the presence of an antigen-presenting cell (APC). An ever-increasing number of cell types have been found to act as APCs; these include macrophages, splenic and lymph node dendritic cells, and Langerhans' cells of the skin. Although activated B lymphocytes and B cell lymphomas are known to serve as APCs, it has been generally believed that resting B cells cannot perform this function. However, in recent studies we have found that resting B cells can indeed present soluble antigen to T cell clones as well as to antigen-primed T cells. The previous difficulty in demonstrating this activity can be explained by the finding that, in contrast to macrophages and dendritic cells, the antigen-presenting ability of resting B cells is very radiosensitive. Macrophages are usually irradiated with 2000-3300 rads to prevent them from incorporating [3H]thymidine in the T cell proliferation assay. Resting B cells, however, begin to lose presenting function at 1500 rads and have completely lost this activity at 3300 rads. It was also possible to distinguish two distinct T cell clonal phenotypes when resting B cells were used as APCs on the basis of two different assays (T cell proliferation, and B cell proliferation resulting from T cell activation). The majority of T cell clones tested were capable of both proliferating themselves and inducing the proliferation of B cells. Some T cells clones, however, could not proliferate in the presence of antigen and B cell APCs, although they were very good at inducing the proliferation of B cells. This suggests that there are two distinct pathways of T cell activation, one leading to T cell proliferation and the other leading only to the release of lymphokines (as measured by the polyclonal activation of B cells).

Animals↗

Antigen presentation by hapten-specific B lymphocytes. IV. Comparative ability of B cells to present specific antigen and anti-immunoglobulin antibody.

The ability of trinitrophenyl (TNP)-binding murine B lymphocytes to present native rabbit IgG (RGG), TNP-modified RGG, and rabbit anti-mouse Ig (RAMG) to an Ia-restricted, RGG-specific helper/inducer T cell clone was compared. By three independent assays (lymphokine secretion, T cell proliferation, and B cell differentiation), TNP-RGG was presented at 10(2)- to 10(3)-fold lower concentrations than RGG, and RAMG at 10(2)- to 10(3)-fold lower concentrations than TNP-RGG. The available data suggest that the efficiency of antigen presentation is dependent primarily on the avidity of binding of a ligand to B cell surface Ig and/or the extent of subsequent endocytosis (modulation). Despite the observed quantitative differences between anti-Ig (RAMG) and specific antigen (TNP-RGG), these results demonstrate that qualitatively both are essentially similar in their ability to mediate specific T-B interactions. Thus, anti-Ig antibodies are valid models for analyzing cognate interactions between antigen-specific B and helper T lymphocytes.

Animals↗

Astrocytes as antigen-presenting cells. I. Induction of Ia antigen expression on astrocytes by T cells via immune interferon and its effect on antigen presentation.

Ia antigens seem to control immune responses on at least two levels. First, they influence the antigen recognition repertoire of the T cells. Second, their variable expression on certain antigen-presenting cells is a powerful regulatory mechanism for the local immune reaction. This is particularly important in the central nervous system (CNS) in which no Ia antigens are normally expressed. Recent experiments in this context have shown that astrocytes are able to express Ia antigens during interaction with T cells, and that they function as antigen-presenting cells. The Ia-inducing activity is produced by activated T cells, and can be replaced by immune interferon (IFN-gamma). In this study we report on the functional and kinetic relationship between Ia antigen expression on astrocytes and the immune-specific activation of T cells by astrocytes. Normal resting astrocytes were found to be negative for Ia antigens by immunofluorescence and by biochemical criteria. Moreover, they are only able to stimulate T cells after they have been induced to express Ia antigens by a signal from the T cells, which is probably mediated by IFN-gamma. In conclusion, the immune-specific interaction between astrocytes and T lymphocytes is a sensitively controlled system that might be pivotal to the development of immune responses in the brain. Malfunction of the system could be an important factor in the pathogenesis of aberrant immune reactions in the CNS, e.g., in multiple sclerosis.

Adjuvants, Immunologic↗

Differential abilities of central nervous system resident endothelial cells and astrocytes to serve as inducible antigen-presenting cells.

Microglial cells and astrocytes are capable of processing and presenting antigens for efficient activation of T cells. However, the antigen-presenting function and role of cerebrovascular endothelial cells (CVEs) in central nervous system inflammatory responses remain controversial. We compared the expression of necessary accessory molecules and the functional antigen-presenting capacity of cloned SJL/J CVEs and primary astrocytes in response to the pro-inflammatory cytokines interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). Astrocytes and CVEs up-regulated major histocompatibility complex (MHC) class II, and primarily B7-1 as opposed to B7-2, in response to IFN-gamma. TNF-alpha inhibited the IFN-gamma-induced up-regulation of MHC class II on CVEs correlating to a decrease in the mRNA for the class II transactivator (CIITA), whereas CIITA expression in astrocytes was unaffected. Unlike astrocytes, CVEs did not elicit significant MHC class II-restricted T-cell responses. Furthermore, we have found that CVE monolayers are altered following T-cell contact, implicating CVE/T-cell contact in the breakdown of the blood-brain barrier during neuro-inflammatory responses.

Animals↗

Cerulenin is a potent inhibitor of antigen processing by antigen-presenting cells.

Cerulenin is an antibiotic that inhibits eukaryotic lipid and sterol synthesis and blocks lipid modification of proteins. The effect of cerulenin on the ability of accessory cells to present antigen to T cells was investigated. This antibiotic strongly inhibits the ability of accessory cells to present antigen to murine T-T hybrids. This effect is observed for multiple distinct antigens including L-glutamic acid60-L-alanine30-L-tyrosine10, bovine insulin, L-glutamic acid56-L-lysine35-L-phenylalanine9, and ovalbumen. Presentation by both macrophage and B lymphoblastoid cell lines is inhibited. The ability to effectively pulse these cells with antigen is inhibited but not the ability of these same cells to present antigen that they have previously processed. Furthermore, this inhibition is selective as it can occur without significant inhibition of the antigen-presenting cell protein or DNA synthesis. Cerulenin does not inhibit antigen uptake or catabolism as assessed with labeled antigen. By these criteria this drug is shown to interfere with an antigen-processing step. The ability of cerulenin to block processing was compared with other known inhibitors. Although cerulenin was effective with all antigens tested, at least one inhibitor was not. Taken together, these results suggest that the effect of cerulenin may define a distinct step in antigen processing and provides evidence that some other processing events are not universally required. The ability of cerulenin to interfere with antigen processing is discussed in the context of the known actions of this antibiotic and events of antigen processing and presentation.

Ammonium Chloride↗

Antigen-presenting cells in the human female reproductive tract: analysis of antigen presentation in pre- and post-menopausal women.

PROBLEM: To determine whether cells in the female reproductive tract (FRT) are functionally capable of presenting antigen to T cells. METHOD OF STUDY: Analysis was done by determining the proliferation of purified autologous T cells to antigen, following co-incubation with non-proliferating cell suspensions isolated from the uterus and prepared by enzymatic digestion of reproductive tract tissues from hysterectomy patients with benign disease. RESULTS: All uterine preparations analyzed were functionally capable of presenting antigen; the ability to present antigen was independent of pre- and post-menopausal status. In contrast, some, but not all, tissues from the ovary, Fallopian tube, cervix, and vagina were capable of presenting antigen. CONCLUSION: These results suggest that the human FRT is an inductive site for immune responses. Regulation of antigen presentation in the reproductive tract may be important for protection against sexually transmitted diseases.

Antigen Presentation↗

Expression of cathepsins B, L, S, and D by gastric epithelial cells implicates them as antigen presenting cells in local immune responses.

Helicobacter pylori infection is linked to chronic gastritis, peptic ulcer and gastric carcinoma. During H. pylori infection, class II MHC expression by the gastric epithelium increases, as does the number of local CD4(+) T cells, which appear to be important in the associated pathogenesis. These observations suggested that the epithelium might present antigens to T cells. Thus, we sought to determine whether gastric epithelial cells process antigens to establish their function as local antigen presenting cells (APC). We examined a panel of gastric epithelial cell lines for expression of the antigen processing cathepsins B (CB), L (CL), S (CS), and D (CD). The mRNA for these enzymes were detected by RT-PCR and the enzymes in the gastric epithelial cells were identified by various independent methods. We corroborated the expression of CB and CD on gastric epithelial cells from human biopsy samples. The functions of these proteases were confirmed by assessing their ability to digest ovalbumin, a conventional dietary antigen, and proteins from H. pylori. In summary, multiple lines of evidence suggest gastric epithelial cells process antigens for presentation to CD4(+) T cells. To our knowledge, these are the first studies to document the antigen processing capacity of human gastric epithelial cells.

Antigen Presentation↗

Defective antigen presentation by lavage cells from terminal patients with cystic fibrosis.

Macrophages separated from lavage samples obtained from lungs removed at transplantation from patients with cystic fibrosis (CF) and other lung diseases, have been compared with circulating monocytes from the same patients for their ability to stimulate allogeneic normal circulating lymphocytes and to present antigen to autologous hilar lymph node cells. In general, macrophages separated from lavage samples from CF patients were unable to stimulate allogeneic lymphocytes and to present antigen, although monocytes from the same patients were functional in both assays. In contrast, lavage cells from non-CF patients were generally effective in both allogeneic stimulation and antigen presentation. These data suggest that immune cells within the lungs of CF patients are functionally compromised, a deficiency which may contribute to the recurrent infections characteristic of the disease.

Antigen Presentation↗

[Antigen presentation of eosinophils in mice].

OBJECTIVE: To explore whether or not eosinophils can present antigen to T lymphocytes in vivo, and to further elucidate the process and characteristics of antigen-presentation by eosinophils in vivo. METHODS: BALB/c mice were sensitized and challenged by ovalbumin to recruit eosinophil infiltration into the airways. The airway eosinophils were purified and were labeled with a fluorescent dye. The labeled eosinophils were instilled into the mouse tracheas, fluorescent microscope was used to observe the migration of endobronchial eosinophils in vivo. Single cell suspension was prepared from paratracheal lymph nodes of mice receiving antigen-exposed eosinophil instillation, and flow cytometry was used to determine proliferation response of T cells and to identify the subset of responding T cells. RESULTS: By 8 h after tracheal instillation, labeled eosinophils were visible in the subcapsular region and streaming through the subcapsular sinus (19.0 +/- 1.8/mm(2)). With increasing time, the numbers of eosinophils entering the regional lymph nodes increased, peaking at 24 h (59.2 +/- 7.2/mm(2)) and persisting for at least 120 h (29.6 +/- 2.8/mm(2)). In sensitized mice that received 5 x 10(5) antigen-exposed eosinophils, in vivo percentage of proliferating T cell in the paratracheal lymph nodes 1 d after eosinophil instillation (6.9% +/- 0.5%) were much higher than basic control value (3.2% +/- 0.3%, P < 0.01), peaked at day 3 (10.8% +/- 0.8%, P < 0.01), and then declined over 7 d (6.1% +/- 0.6%, P < 0.05). Eosinophil-induced in vivo T cell proliferation was antigen-specific, and the responding T cells were limited to CD4(+) cells. CONCLUSIONS: Eosinophils within the lumina of airways can process inhaled antigens, traffick to regional lymph nodes and function in vivo as antigen-presenting cells to stimulate responses of CD4(+) T cells.

Animals↗

B cells carrying surrogate receptors in their membranes process and present antigen to specific murine T cells.

A palmitate-conjugate derivative of ovalbumin which can be inserted into the membrane of B cells has been prepared. The ability of these cells to act as antigen-presenting cells for specific T lymphocytes obtained from immunized mice was tested. It was found that the conjugates were more efficiently processed and presented than the naive form of the antigen. Palmitate-conjugated antibodies specific to ovalbumin were also inserted into the cell membrane of normal B lymphocytes. These cells were pulsed with the antigen and tested as antigen-presenting cells for T cells obtained from immunized mice. The antibody-decorated B cells presented ovalbumin more efficiently than non-decorated controls. Whether antibody-decorated, antigen-pulsed B cells could prime T cells in vivo was investigated. Some priming activity was found.

Animals↗

Antigen presentation to T cell hybridomas by a macrophage cell line: an inducible function.

We have investigated the ability of an Ia-, nonantigen-presenting macrophage tumor cell line, P388D, (H-2d), to present antigen to T cell hybridomas after incubation in a lymphokine-containing preparation. P388D, cells were incubated in microtiter wells with various concentrations of Con A-stimulated spleen cell supernatants. Antigen-specific stimulation of H-2d-restricted, KLH-specific T cell hybridomas was observed by P388D1 incubated with SUP.P388D1 cells incubated for 3 days in medium or control SUP did not present antigen. In addition, no stimulation of T hybridomas was seen by P388D1 in the inhibited by the appropriate monoclonal anti-Ia reagents. These results demonstrate that a macrophage tumor cell line can be induced to present antigen and provides for large numbers of readily available, homogeneous macrophages for studying the cellular biochemical requirements for antigen processing and presentation.

Antigens↗

Human primary and memory cytotoxic T lymphocyte responses are efficiently induced by means of CD40-activated B cells as antigen-presenting cells: potential for clinical application.

CD40 engagement is the major signal that induces B cells to efficiently present antigen to T cells. We previously demonstrated that human peripheral blood-derived CD40-activated B cells (CD40-B cells) function as antigen-presenting cells (APCs). Here, we have established a culture system to generate these APCs under clinically applicable conditions using guanylic acid-grade soluble trimeric CD40 ligand. To monitor APC function and antigen loading for these cells, simple and efficient quality control assays have been developed. Using this approach, we demonstrate that CD40-B cells from healthy donors and cancer patients are fully functional and equally expanded in long-term cultures. These B cells boost robust memory T-cell responses, but more importantly, they also prime naive T-cell responses against neoantigens ex vivo. CD40-B cells overcome current obstacles, such as the difficulty of isolation, generation, and long-term expansion observed with other APCs. Therefore, they are an excellent source of professional APCs for immune assessment, antigen discovery, and antigen-specific immunotherapy.

Adult↗

B cells as antigen presenting cells.

Several characteristics confer on B cells the ability to present antigen efficiently: (1) they can find T cells in secondary lymphoid organs shortly after antigen entrance, (2) BCR-mediated endocytosis allows them to concentrate small amounts of specific antigen, and (3) BCR signaling and HLA-DO expression direct their antigen processing machinery to favor presentation of antigens internalized through the BCR. When presenting antigen in a resting state, B cells can induce T cell tolerance. On the other hand, activation by antigen and T cell help converts them into APC capable of promoting immune responses. Presentation of self antigens by B cells is important in the development of autoimmune diseases, while presentation of tumor antigens is being used in vaccine strategies to generate immunity. Thus, detailed understanding of the antigen presenting function of B cells can lead to their use for the generation or inhibition of immune responses.

Animals↗

Impaired antigen presentation by splenocytes of ethanol-consuming C57BL/6 mice.

Excessive alcohol consumption impairs T-cell-dependent immune function. Whether this impairment results from the direct inhibition of helper T (Th) cells or from inhibition of the cells that process and present antigen to Th cells is unclear. The present study examines the effect of dietary alcohol on the ability of spleen cells from C57BL/6 mice to present antigen to T-cell hybridomas. We find that ethanol consumption impairs the ability of spleen cells to present hen egg lysozyme (HEL) in vitro. This impairment was seen for native HEL protein, a hapten-modified HEL, and a peptide bearing a minimal T-cell epitope (HEL 51-60) that requires no additional enzymatic processing. These results suggest that deficiencies in immune responsiveness in alcohol-consuming individuals may include antigen presentation.

Alcohol Drinking↗

Perivascular microglial cells of the CNS are bone marrow-derived and present antigen in vivo.

A crucial question in the study of immunological reactions in the central nervous system (CNS) concerns the identity of the parenchymal cells that function as the antigen-presenting cells in that organ. Rat bone marrow chimeras and encephalitogenic, major histocompatability--restricted T-helper lymphocytes were used to show that a subset of endogenous CNS cells, commonly termed "perivascular microglial cells," is bone marrow-derived. In addition, these perivascular cells are fully competent to present antigen to lymphocytes in an appropriately restricted manner. These findings are important for bone marrow transplantation and for neuroimmunological diseases such as multiple sclerosis.

Animals↗

In vivo antigen presentation.

Monoclonal antibodies specific for defined peptide-MHC complexes are now being used to physically detect T-cell receptor ligands. These reagents have resulted in the identification of the cells that present antigen in lymphoid and non-lymphoid tissues after various forms of antigen administration. In addition, recent advances in real-time imaging technology have begun to measure the rate and directionality of T-cell movement relative to antigen-presenting cells in lymph nodes, shedding light on the earliest events in T-cell activation in a physiological setting.

Adjuvants, Immunologic↗

Differential lysosomal proteolysis in antigen-presenting cells determines antigen fate.

Antigen-presenting cells (APCs) internalize antigens and present antigen-derived peptides to T cells. Although APCs have been thought to exhibit a well-developed capacity for lysosomal proteolysis, here we found that they can exhibit two distinct strategies upon antigen encounter. Whereas macrophages contained high levels of lysosomal proteases and rapidly degraded internalized proteins, dendritic cells (DCs) and B lymphocytes were protease-poor, resulting in a limited capacity for lysosomal degradation. Consistent with these findings, DCs in vivo degraded internalized antigens slowly and thus retained antigen in lymphoid organs for extended periods. Limited lysosomal proteolysis also favored antigen presentation. These results help explain why DCs are able to efficiently accumulate, process, and disseminate antigens and microbes systemically for purposes of tolerance and immunity.

Animals↗