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Results for “antigen presentation”

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PubMed1983

Antigen-presenting capabilities of human monocytes correlates with their expression of HLA-DS, an Ia determinant distinct from HLA-DR.

Utilizing a monoclonal antibody (Mac-120) specific for 40 to 60% of peripheral blood adherent mononuclear cells (M phi), we were able to separate M phi into two populations based on their reactivity with the antibody. Both populations, Mac-120+ and Mac-120- cells, were then compared for a) their ability to present antigen to T cells, b) their display of HLA-DR determinants, c) their ability to stimulate in an autologous and allogeneic mixed lymphocyte reaction, and d) their display of an Ia molecule, HLA-DS, which is distinct from HLA-DR and which is homologous with murine I-A. Our findings indicate that a) only Mac-120+ cells can present antigen, b) Mac-120+ and Mac-120- cell populations are equivalent in terms of the number of HLA-DR+ cells and in the mean density of HLA-DR determinants per cell, c) although Mac-120+ and Mac-120- cells are equivalent in their ability to serve as stimulators in an allogeneic mixed lymphocyte reaction, Mac-120+ cells are better stimulators in an autologous mixed lymphocyte reaction, and d) only Mac-120+ cells display HLA-DS. These studies demonstrate that peripheral adherent mononuclear cells exhibit heterogeneity with regard to their display of Ia antigens. Furthermore, they provide functional data to support the existence of a human Ia determinant, HLA-DS, which is distinct from HLA-DR and which is important in antigen presentation and stimulation in the autologous mixed lymphocyte reaction.

Amino Acid Sequence↗

PubMed1995

Mouse microglial cell lines differing in constitutive and interferon-gamma-inducible antigen-presenting activities for naive and memory CD4+ and CD8+ T cells.

We developed a panel of non-virus transformed cell lines derived from individual microglial precursors residing in the brains of normal mice. These colony stimulating factor-1-dependent cell lines are B7-1+ (CD80), Mac-1+, Mac-2+, Mac-3+, CD45+, MHC class I+, colony stimulating factor-1 receptor+, and they ingest antibody-coated particles. However, the cell lines differ in their expression of B7-2 (CD86), F4/80, Ly-6C and MHC class II molecules. They also differ in their ability to constitutively process and present antigens to naive CD4+ and CD8+ T cells, memory CD4+ and CD8+, and in the manner by which interferon gamma modulates their antigen-presenting activities. These cell lines should be valuable as models for studies on the immunobiology of the microglia.

Adjuvants, Immunologic↗

PubMed1995

IL-10 inhibits tumor antigen presentation by epidermal antigen-presenting cells.

IL-10 inhibits Langerhans cell (LC) Ag presentation to Th1 clones. As LC are capable of presenting tumor-associated Ags (TAA) for primary and secondary tumor immune responses, we examined the effect of IL-10 on LC Ag presentation in a model of immunity to the S1509a spindle cell tumor (H-2a). Because induction of immunity to S1509a requires exposure of LC to granulocyte-macrophage (GM)-CSF, this system also allowed us to study the regulatory interactions of GM-CSF and IL-10 on LC. Naive CAF1 (H-2a/d) mice could be immunized against S1509a by injection with GM-CSF-exposed and TAA-pulsed epidermal cells (EC) as assessed by inhibition of the growth of inoculated tumor cells. Incubation of EC in IL-10 before GM-CSF exposure completely inhibited Ag presentation in this system. Significantly, neither co-incubation of EC in IL-10 and GM-CSF (without preincubation in IL-10) nor IL-10 treatment after GM-CSF incubation was able to exert a down-regulatory effect. The ability of IL-10 to modulate EC presentation of TAA for a secondary immune response was also examined. EC were pulsed with TAA in vitro and then injected into a hind footpad of tumor-immune mice with 24 h swelling assessed as a measure of delayed-type hypersensitivity. Preincubation in IL-10 before TAA exposure significantly inhibited elicitation of delayed-type hypersensitivity with or without subsequent exposure to GM-CSF. Co-incubation of EC in IL-10 and GM-CSF or exposure to IL-10 after GM-CSF led to a normal response. These data indicate that IL-10 may serve as an important regulator of LC Ag-presenting function for tumor immune responses. IL-10 appears to specifically prevent the GM-CSF-induced maturation of LC Ag-presenting function when treatment with IL-10 occurs before exposure to GM-CSF but does not reverse the established mature state.

Animals↗

PubMed1994

Rat peritoneal mast cells present antigen to a PPD-specific T cell line.

Rat peritoneal mast cells were examined to determine whether mast cells can stimulate T cell proliferation through antigen presentation. Mast cells were obtained by peritoneal lavage and purified to 98% using density gradient centrifugation. Purified peritoneal mast cells expressed MHC class II molecules as determined by flow cytometry using monoclonal antibody OX6 specific for common determinants of rat class II. The intensity of class II expression by mast cells was not significantly increased upon incubation with recombinant rat IFN-gamma. Peritoneal mast cells also were found to express the accessory molecules ICAM-1 (CD54) and LFA-1 beta (CD18) but not LFA-1 alpha (CD11a). In the presence of antigen, purified mast cells stimulated proliferation of an autologous CD4+, PPD-specific T cell line. This stimulation was blocked by OX6 antibody, confirming that the proliferation was class II dependent. T cell proliferation was similarly induced by purified mast cell populations that were completely monocyte and macrophages depleted. These results demonstrate that mast cells, through their expression of MHC class II and accessory molecules, are capable of antigen presentation.

Animals↗

PubMed1989

Efficiency of antigen presentation after antigen targeting to surface IgD, IgM, MHC, Fc gamma RII, and B220 molecules on murine splenic B cells.

Bispecific heteroconjugate antibodies can bind soluble protein Ag to APC and thereby enhance Ag presentation. We used such antibodies to bind hen egg lysozyme (HEL) to various structures on the surface of normal splenic B cells to determine which structures would provide the best targets for enhanced presentation. We found that HEL was presented efficiently to hybridoma T cells if bound to sIgD, sIgM, or class I or II MHC molecules, but not at all if bound to Fc gamma RII, or B220 molecules on B cells. The efficiency of presentation of HEL was measured as a function of the amount of 125I-HEL bound per cell. HEL was presented with 5 to 10 times greater efficiency when bound to sIg, than when bound to MHC molecules. When compared on the basis of the amount of HEL bound, sIgD and sIgM functioned equally as target structures, as did class I and class II MHC molecules. Large amounts of HEL bound to B220, but no presentation resulted, indicating that focusing HEL to the APC surface was not sufficient for presentation to occur. HEL was internalized rapidly and in large amounts when bound to sIgD or sIgM, but slowly and in small amounts, when bound to class I or class II MHC molecules. Thus, a rapid rate of internalization may in part explain the high efficiency of Ag presentation after binding to sIg. However, the small amount of HEL internalized via MHC molecules was utilized efficiently for presentation. These results indicate that sIgM and sIgD serve equally on normal B cells to focus and internalize Ag and enhance Ag presentation, but that class I or class II MHC molecules can also be used to internalize Ag and enhance Ag presentation, perhaps by a separate intracellular processing pathway.

Animals↗

PubMed1995

Characterization of defectiveness in endogenous antigen presentation of novel murine cells established from methylcholanthrene-induced fibrosarcomas.

Three cell lines (4A1, 4C2 and 6D1 cells) derived from fibrosarcoma induced by the inoculation of 3-methylcholanthrene into C3H/HeN (H-2k) mice were examined for their ability to present antigens to CD8+ cytotoxic T lymphocytes (CTL). 6D1 and 4C2 cells were deficient in presenting endogenously synthesized influenza virus antigens to CTL, but they were able to present antigens when they were sensitized with a synthetic epitope peptide. The expression of the H-2 Kk gene in 4C2 and 6D1 cells was much reduced and was detectable only with Northern blot hybridization. The expression of two transporter genes (TAP1 and TAP2), examined by Northern hybridization, was also reduced in both cells, and negligible particularly in 4C2 cells. Interferon-gamma (IFN-gamma) treatment of these cells induced expression of Kk, TAP1 and TAP2 genes and rescued the defect of class I-restricted antigen presentation in 4C2 and 6D1 cells. Even after this treatment, however, antigen-presentation capability of 4C2 cells was still much lower than that of normal 4A1 cells. This finding suggests that 4C2 cells might have an additional defective gene(s), whose products are involved in the processing of class I-restricted antigen, besides the Kk and TAP genes, and this may explain the difficulty of 4C2 cells to induce tumour-specific immunity, as described previously. To our knowledge, the 4C2 cell is the first tumour cell postulated to have more than three defective genes involved in class I-restricted antigen presentation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1994

Antigen presentation by major histocompatibility complex class I-B molecules.

Class I-b genes constitute the majority of MHC class I loci. These monomorphic or oligomorphic molecules have been described in many organisms; they are best characterized in the mouse, which contains a substantial number of potentially intact genes. Two main characteristics differentiate class I-b from class I-a molecules: limited polymorphism and lower cell surface expression. These distinguishing features suggest possible generalizations regarding the evolution and function of this class. Additionally, class I-b proteins tend to have shorter cytoplasmic domains or in some cases may be secreted or may substitute a lipid anchor for the transmembrane domain. Some are also expressed in a limited distribution of cells or tissues. At least six mouse MHC class I-b molecules have been shown to present antigens to alpha beta or gamma delta T cells. Recent advances have provided insight into the physiological function of H-2M3a and have defined the natural peptide-binding motif of Qa-2. In addition, significant progress has been made toward better understanding of other class I-b molecules, including Qa-1, TL, HLA-E, HLA-G, and the MHC-unlinked class I molecule CD1. We begin this review, however, by arguing that the dichotomous categorization of MHC genes as class I-a and I-b is conceptually misleading, despite its historical basis and practical usefulness. With these reservations in mind, we then discuss antigen presentation by MHC class I-b molecules with particular attention to their structure, polymorphism, requirements for peptide antigen binding and tissue expression.

Amino Acid Sequence↗

PubMed1993

Characterization of antigen-presenting cells that present exogenous antigens in association with class I MHC molecules.

Exogenous Ag in the extracellular fluids do not gain access to the class I Ag-presenting pathway in most cells. However, there is an APC resident in spleen that can process and present exogenous Ag in association with class I molecules. We characterize the phenotype of this cell. This APC is of low buoyant density, is adherent to Sepharose and glass, and expresses both class II molecules and FcR. This phenotype identifies this APC as a macrophage. Resident, peptone- and thioglycolate-induced peritoneal macrophages also display this Ag-presenting activity. Analysis with CTL clones suggest that this Ag-presenting pathway may be active in only a subset of macrophages. A similar Ag-presenting activity is also present in dendritic cell-enriched populations from spleen although we cannot rule out the possible involvement of contaminating macrophages. In contrast, B and T cells that are resident in spleen and LPS blasts are unable to present exogenous Ag in association with class I molecules. The presentation of exogenous OVA with class I molecules is not inhibited by the inhibitors of thiol proteases, leupeptin, and antipain. The presence of gelonin, a ribosomal inactivating protein, in the extracellular fluids inhibits the ability of these APC to present exogenous OVA. Under identical conditions, gelonin does not inhibit Con A-stimulated T cell proliferation, or LPS-stimulated B cell proliferation and Ag presentation. These results are discussed in relation to the potential pathways through which an Ag in the extracellular fluids is presented with MHC class I molecules.

Animals↗

PubMed1999

Exercise suppresses macrophage antigen presentation.

This study determined the effects of exercise on the ability of macrophages (Mphi) to present antigen to T cells. Pathogen-free male Balb/c mice (8 +/- 2 wk of age) were randomly assigned to either home cage control, moderate exercise (Mod; 18 m/min, 5% grade, 0.5 h/day), exhaustive exercise (Exh, 18-30 m/min, 3 h/day), or treadmill control groups. The mice underwent treatments for 4 days during peritoneal thioglycolate inflammation. Peritoneal Mphi were harvested, purified, and incubated with chicken ovalbumin (C-OVA; 0-10 mg/ml) for 18 h. Mphi were then cocultured with C-OVA-specific T cells for 48 h, and the supernatants were analyzed via ELISA for interleukin-2 as an indication of Mphi antigen presentation (AP). Exh exhibited suppressed ( approximately 25-34%) Mphi AP across a wide range of C-OVA doses when measured immediately, 3, and 24 h postexercise. In contrast, Mod had reduced Mphi AP only at 3 h postexercise. Mphi AP was also lower in the treadmill control (4-27%) compared with the home cage control group, but was significantly higher than Exh. The reduction in Mphi AP was not due to exercise-induced differences in Mphi number, percentage, or expression of intercellular adhesion molecule-1, B7-2, or major histocompatability complex II, molecules important in AP. In conclusion, our data lend evidence that may help explain the increased incidence of infection observed after prolonged exhaustive exercise or overtraining.

Animals↗

PubMed1992

Murine bladder carcinoma cells present antigen to BCG-specific CD4+ T-cells.

Intravesical administration of Bacillus Calmette-Guérin (BCG) is the most effective therapy for superficial transitional cell carcinoma of the bladder although its mechanism of action is not known. To determine if bladder tumors are capable of antigen presentation and thus might interact directly with BCG-specific T-cells, we studied the murine bladder tumor MB49. MB49 (MHC Class II negative) (IA-), when induced to express IA with interferon, presented BCG to specific CD4+ T-cells obtained from bladder-draining lymph nodes following intravesical BCG administration. This interaction resulted in antigen- and IA-dependent interleukin 2 and tumor necrosis factor production. Interferon also induced MB49 IA expression in vivo. This first demonstration of antigen presentation by epithelial tumors supports new approaches to immunotherapy of these malignancies.

Administration, Intravesical↗

PubMed1985

Investigations into the mechanism of immunosuppression caused by acute treatment with O,O,S-trimethyl phosphorothioate. II. Effect on the ability of murine macrophages to present antigen.

Acute administration of 10 mg/kg O,O,S-trimethyl phosphorothioate (OOS-TMP) for 24 h has been shown to suppress the in vitro generation of cytotoxic T lymphocyte responses and antibody-secreting cells to sheep red blood cells and to increase interleukin-2 production. Macrophages were shown to be the splenic cell population most affected by OOS-TMP pretreatment. In this report, the ability of macrophages from OOS-TMP-treated animals to function in antigen presentation was shown to be significantly decreased. In addition, macrophages from treated animals had increased phagocytic capability and interleukin-l production. However, the percentage of Ia-positive macrophages present in splenic populations was decreased following OOS-TMP treatment. A decrease in antigen presenting ability and the number of Ia-positive macrophages may explain the reversible suppression in cytotoxic T lymphocytes and antibody responses reported previously.

Animals↗

PubMed1985

The beta 1 domain of the mouse E beta chain is important for restricted antigen presentation to helper T-cell hybridomas.

We have constructed a hybrid E beta gene by replacing the second exon of the Ed beta gene (which encodes the majority of the beta 1 protein domain) with the corresponding exon from the Eb beta gene. The hybrid gene has been introduced into a d haplotype host, the lymphoma beta-cell line A20-2J, and an E alpha E beta dimer composed of the endogenous Ed alpha chain and the product of the hybrid Ed beta/Eb beta gene was immunoprecipitated from extracts of transfected cells with an Ed alpha Eb beta-specific monoclonal antibody. Transfected cells have acquired the ability to present antigen to Ed alpha Eb beta-restricted helper T-cell hybridomas, indicating that the second exon of the gene for the E beta chain encodes sequences required for the restricted recognition of the antigen-presenting cell by the class II-restricted responder T-cell.

Animals↗

PubMed1989

Direct binding of a myasthenia gravis related epitope to MHC class II molecules on living murine antigen-presenting cells.

MHC gene products present antigenic epitopes to the antigen receptor on T cells. Nevertheless, direct binding of such epitopes to MHC class II proteins on normal living antigen-presenting cells (APCs) has not yet been demonstrated. We have previously shown a significant difference in the ability of T cells of myasthenia gravis (MG) patients to proliferate in response to the synthetic peptide p195-212 of the human acetylcholine receptor (AChR) alpha-subunit in comparison to healthy controls. The observed proliferative responses correlated significantly with HLA-DR5. Moreover, lymph node cells of various mouse strains that were primed with the T cell epitope, p195-212, were found to proliferate to different extents. To investigate these observations further, we designed an assay for direct binding of p195-212 to MHC class II proteins on the surface of freshly prepared splenic adherent cells. Binding of a biotinylated p195-212 was monitored using phycoerythrin-avidin by flow cytometry. Fifteen to sixty per cent of the cells were labeled following incubation with the biotinylated peptide. Binding was observed only to splenic adherent cells derived from mouse strains of which T cells were capable of proliferating in response to p195-212. The binding specificity, in terms of epitope structure and its site of interaction on the cells, was shown by its inhibition with an excess of the unlabeled peptide or with the relevant monoclonal anti-I-A antibodies. These results constitute the first direct evidence for the specific binding of a T cell epitope to live APC.

Amino Acid Sequence↗

PubMed1985

Generation of functional I-Ed variants from an antigen-presenting macrophage cell line.

We report the ability of the BAC1.2 macrophage cell line to present antigen both to populations of antigen-primed lymph node cells and to T cell hybridomas. We also describe the selection of I-Ed variants derived from this cell line. These variants have lost the ability to present antigen to an I-Ed plus ovalbumin-specific T cell line, but retain the ability to stimulate an I-Ad plus ovalbumin-restricted T cell line, and a T cell line reactive with I-Ed alone. These variants should aid in the elucidation of structural elements of the I-E molecule involved in the interaction with helper T cells.

Animals↗

PubMedDate not supplied

Dendritic cells produce eicosanoids, which modulate generation and functions of antigen-presenting cells.

Eicosanoids have been shown to be potent immunoregulatory arachidonic acid (AA) metabolites. AA is the precursor of prostaglandin E(2) (PGE(2)) and leukotriene B(4) (LTB(4)) which are able to modulate both inflammation and the immune response. Dendritic cells process and present antigens to T lymphocytes. They are highly specialized antigen-presenting cells (APC) and usually considered as 'professional APC'. In the present paper, we report some data on the biosynthetic capacity of murine APC from the bone marrow (BM-DCs) to produce AA metabolites. Using an ELISA we have observed that BM-DCs spontaneously produce both PGE(2) and LTB(4) whose production increased in response to bacterial lipopolysaccharides (LPS). In addition we found that LTB(4) production was twice as high when both COX pathways were blocked with selective COX-inhibitors. We have also investigated the effect of PGE(2) and LTB(4) on the in vitro generation of the so-called BM-DCs. Exogenous PGE(2) and LTB(4) added to bone marrow cultures inhibit and promote, respectively, BM-DC generation. PGE(2) added to the maturing BM-DCs reduces their MHC class-II expression.

Animals↗

PubMed1985

Antigen presentation by proliferating thymic macrophages to A (T,G)-A-L specific T cell line in an H-2 restricted manner.

Long-term cultures of murine homogeneous populations of Ia-bearing thymus-derived murine macrophages were tested for their ability to present antigen to a (T,G)-A-L specific IL-2-dependent continuous T cell line. Thymus-derived macrophages, with and without pretreatment for Ia induction, triggered efficiently antigen-specific T cell proliferation in an MHC restricted way. This experimental system, consisting of two normal proliferating homogeneous populations of macrophages and antigen specific T cells, provides an ideal tool for studying the mechanism of antigen presentation to T cells and for elucidation of the role of macrophages in T-B cell collaboration for antibody production.

Animals↗

PubMed1993

A mutant antigen-presenting cell defective in antigen presentation expresses class II MHC molecules with an altered conformation.

Ag presentation by APC to class II MHC-restricted T cells involves a sequence of events: 1) intracellular processing of protein Ag into immunogenic peptides, 2) specific binding of peptides to class II MHC molecules, and then 3) transport of the MHC-peptide complexes to the plasma membrane. The critical event in the activation of T cells by APC is the recognition of MHC-associated antigenic determinants by the TCR/CD3 complex. In this report we describe the isolation and characterization of a mutant APC with a defect in an intracellular process that results in its inability to form MHC-peptide complexes for recognition by T cells. The mutant APC cannot present many different protein Ag with both I-A and I-E molecules but is able to present processing-independent peptides. The functional defect in the mutant APC is not caused by either a decrease in expression or a structural mutation in class II MHC molecules. Further, there is no mutation in the invariant chain (li) and it displays a normal kinetics of association and dissociation from the class II MHC molecules during biosynthesis. Although the mutation is not in the genes encoding for the class II MHC molecules or li, the mutant APC expresses class II MHC molecules with distinct serological epitopes suggestive of an altered conformation. Pulse-chase experiments suggest that a conformational difference between I-Ad molecules of wild-type and mutant cells occurs after the class II molecules exit from the endoplasmic reticulum but while they are still associated with li. The mutant cell produces few compact (SDS-resistant) class II heterodimers. This mutant APC provides a tool for studying the cell biology of Ag processing and presentation.

Animals↗

PubMed1991

Differential regulation of antigen presentation in high- and low-IgE responder mice.

Strains of mice differ greatly in their capacity to produce interleukin (IL) 4 and high levels of serum IgE. The contribution of macrophages (M phi) in enhancing the production of IL4 by T cells in high-IgE responder mice was studied. M phi from BALB/c mice (high-IgE responder strain) developed an augmented capacity to present antigen to IL 4-producing T helper type 2 (Th2) clones, when the M phi were pretreated by exposure to the lymphokines IL 4 and IL 5. In contrast, identical treatment of M phi from H-2-identical DBA/2 mice (low-IgE responder strain) resulted in inhibition of the capacity to stimulate Th2 clones. The impairment of antigen presentation by DBA/2 M phi was closely paralleled by a decrease of cell surface class II major histocompatibility complex (MHC) expression and an abrogation of IL 1 production by these cells, while identical treatment of BALB/c M phi enhanced class II MHC expression and did not inhibit secretion of IL 1. Our studies demonstrate that IL 4 and IL 5 can exert different effects on M phi from high- and low-IgE responder strains of mice, resulting in down-regulation of the expansion of IL 4-producing cells in low-but not high-IgE responder mice.

Animals↗