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At least 19 recordsLinked to original sources
PubMed1981

Immunogenicity of allograft components. III. Immunogenic components in the rat heart allografts and reduction of immunogenicity of leukocytes by pretreatment of the cell donor.

Enzymatically disaggregated DA hearts were fractionated into three components, one isolated for endothelial cells, another for myocardial cells and the third for passenger cells. Cells of each component were used separately to prime AgB-incompatible AO recipients in the "primed rejection assay", PRA. The primed recipients were transplanted 72 hours later with a DA heart allograft. Only cells of the passenger-enriched component induced accelerated rejection, indicating that the most immunogenic component in rat heart is indeed, the passenger population. DA spleen cells were then used to simulate the passenger cells in an attempt to elucidate the mechanisms of survival prolongation by donor pretreatment. DA strain rats were pretreated with different cytotoxic drugs known to prolong strongly, moderately or not at all the survival of a heart allograft by donor pretreatment. Their spleen cells were harvested 6 hours later and used either (a) to prime AO recipients for the PRA or (b) as stimulator cells in one-way mixed lymphocyte culture. With one exception, the drugs capable of prolonging graft survival failed to induce accelerated rejection and were non-stimulating or only weakly stimulating in the MLC. The drug pretreatment did not significantly alter the survival of stimulator cells in vitro. In summary, the results are compatible with an earlier hypothesis that donor pretreatment primarily affects the passenger leukocyte component of the organ allograft by reducing its immunogenicity.

Animals↗
PubMed1979

Macrophage-T cell interaction mediated by immunogenic and non-immunogenic forms of a monofunctional antigen.

As an approach to the elucidation of the essential steps in the immune pathway, the uptake and retention of immunogenic and non-immunogenic analogs of a monofunctional antigen by guinea pig macrophages and the efficiency of macrophages pulsed with the compounds to present antigen to sensitized T lymphocytes were compared. L-Tyrosine-azobenzene-p-arsonate (RAT) and its non-immunogenic analog, 4-hydroxyphenyl-n-propane-3-azobenzene-p-arsonate (RAN), react similarly with antiarsonate antibody, but RAN, unlike RAT, is unable to induce cellular immunity in guinea pigs. The uptake and retention patterns of the two compounds by macrophages differed in that, at a given time, more RAN than RAT was retained and detectable on cell surfaces by anti-arsonate antibody. Equivalent numbers of T lymphocytes from guinea pigs sensitized to RAT formed antigen-dependent clusters with macrophages pulsed with either RAT or RAN after 24 hr in culture, but not with macrophages pulsed with an azobenzenoid compound of unrelated specificity. On the other hand, T lymphocytes from guinea pigs immunized with RAN showed no significant capacity to bind to macrophages which had been pulsed with any of the compounds. The number of lymphocytes from RAT-sensitized animals which bound to RAT-pulsed macrophages remained relatively stable over a 48 hr period, whereas clusters of the same lymphocytes with RAN-pulsed macrophages dissocitated to background levels within that time. Early cluster formation mediated by RAN, as well as its ability to induce transient specific T cell unresponsiveness to RAT in vivo, indicate that T cells are capable of recognizing (binding) the non-immunogen. However, such early, and perhaps weak, interaction with RAN-pulsed macrophages did not induce DNA synthesis by T cells. Anti-Ia serum completely blocked cluster formation mediated by either RAT or RAN. Thus, the only significant distinction disclosed by these studies between the immunogenic and non-immunogenic compounds was the stability of macrophage-T cell interaction as determined by the persistence of antigen mediated cell clusters in culture, suggesting that this may be a factor in immunogenic discrimination.

Animals↗
PubMed1998

Safety and immunogenicity of an HLA-based HIV envelope polyvalent synthetic peptide immunogen. DATRI 010 Study Group. Division of AIDS Treatment Research Initiative.

OBJECTIVE: To evaluate the safety and immunogenicity of a polyvalent (PV) HIV envelope synthetic peptide immunogen, C4-V3. The immunogen comprised four peptides containing T-helper epitopes from the fourth constant region (C4) of gp120 of HIV-1MN, and T-helper, cytotoxic T-lymphocyte HLA-B7-restricted, and B-cell neutralizing epitopes from the gp120 third variable region (V3) of four clade B HIV-1 isolates, HIV-1MN, HIV-1RF, HIV-1EV91, and HIV-1Can0A. DESIGN: A pilot, Phase I controlled trial [Division of AIDS Treatment Research Initiative (DATRI) 010] conducted at a single center. METHODS: Ten HIV-infected, HLA-B7-positive patients with CD4 cells > 500 x 10(6)/l were enrolled. Eight patients received the C4-V3 PV immunogen emulsified in incomplete Freund's adjuvant in five intramuscular injections over 24 weeks, and two controls received incomplete Freund's adjuvant alone. All subjects were followed for 52 weeks. RESULTS: Four out of eight C4-V3 PV recipients generated at least fourfold rise in serum antibody titers to at least three immunogen peptides in contrast to none of the control subjects. Four out of eight C4-V3 PV recipients and none of the controls had an at least fourfold rise in neutralizing antibodies to either HIV-1MN, HIV-1RF, or HIV-1(4489-5) laboratory-adapted HIV isolates. 3H-Thymidine incorporation assays of peripheral blood mononuclear cells increased at least fivefold over the baseline stimulation index to at least one of the immunogen peptides in two consecutive post-immunization timepoints in five out of eight C4-V3 PV recipients versus none of the controls. CD4 cell counts and plasma HIV RNA levels did not change in patients who received either C4-V3 PV or adjuvant alone. Adverse events consisted primarily of grade 1 injection site reactions in six subjects (four C4-V3 recipients, two controls). CONCLUSIONS: C4-V3 PV synthetic peptides demonstrated both immunogenicity and safety in HIV-infected patients.

AIDS Vaccines↗
PubMed2006

[Conjugation and immunogenic evaluation of complete immunogen for the small molecular environmental pollutants 2,4-D].

Conjugation of complete immunogen for 2,4-dichlorophenoxyacetic acid (2,4-D) was studied. 2,4-D was cross-linked to bovine serum albumin (BSA, carrier) by 1-ethyl-3-(3-dimethyl- aminopropyl) carbodiimide hydrochloride (EDC). The conjugation reaction was found to be more effective at 4 degrees C and incubated for 18 hour. 2,4-D was dissolved in 0.05 mol/L phosphate buffer between 10.0 - 12.0 mg/mL concentration, pH was adjusted to be 5.4 - 6.1. When the weight of added EDC was below 12 mg, the more EDC was added the higher substitution degree complete immunogen was synthesized. Complete immunogen of various substitution degree (2,4-D: protein) were applied to immunize balb/c mice. The conjugates of 2,4-D and poly-L-lysine was applied as coating antigen. It was experimentally found that complete immunogen of substitution degree 12 and 18 are more immunogenic than that of substitution degree 6 and 25. None-specific adsorption between antiserum that was produced by complete immunogen of substitution degree 18 and coating antigen was very weak, and the antiserum contained more 2,4-D specific antibody. It could be used as the immunogen for the preparation monoclonal antibody.

2,4-Dichlorophenoxyacetic Acid↗
PubMed1996

A serum-mediated mechanism for concomitant resistance shared by immunogenic and non-immunogenic murine tumours.

Resistance of tumour-bearing mice to a second tumour challenge, that is concomitant resistance, was evaluated in euthymic and nude mice using nine tumours with widely different degrees of immunogenicity. Two temporally separate peaks of concomitant resistance were detected during tumour development. The first one was exhibited only by small immunogenic tumours; it was tumour specific and mediated by classical immunological T-cell-dependent mechanisms. The second peak was shared by both immunogenic and non-immunogenic large tumours; it was non-specific, thymus independent and correlated with the activity of a serum factor (neither antibody nor complement) that inhibited the in vitro proliferation of tumour cells. This factor was eluted from a Sephadex G-15 column at fractions corresponding to a molecular weight of approximately 1000 Da and it was recovered from a high-performance liquid chromatography column in one peak presenting maximum absorption at 215 and 266 nm. The data presented in this paper suggest for the first time, to our knowledge, that in spite of the differences between immunogenic and non-immunogenic tumours, a common serum-mediated mechanism seems to underlie the concomitant resistance induced by both types of tumours at late stages of tumour development.

Adenocarcinoma↗
PubMed2000

B7.1 expression by the weakly immunogenic F98 rat glioma does not enhance immunogenicity.

Enhanced immunogenicity has been reported following transfection of a variety of immunogenic tumors with the B7.1 co-stimulatory molecule. The purpose of the present study was to determine if transfection of a weakly immunogenic rat brain tumor, the F98 glioma, with the gene encoding B7.1 could enhance its immunogenicity. F98 cells were transfected with a plasmid containing the B7.1 gene, and stable transfectants (F98/B7.1) were obtained. Flow cytometric analysis confirmed the expression of B7.1 and MHC class I antigens on the cell surface. To investigate the effects of B7.1 expression on the tumorigenicity of the F98 glioma, Fischer rats were implanted intracerebrally with either F98 (wild-type) or F98/B7.1 transfected cells. No significant differences in survival times were noted. Mean survival times of 21.8 and 24.0 days were observed for the respective groups at a challenge dose of 103 cells. These differences in survival time were not significant. To determine if expression of B7.1 enhanced the immunogenicity of the F98 glioma, rats were vaccinated weekly for 3 weeks with 107 mitomycin C-treated F98 or F98/B7.1 cells injected subcutaneously and then challenged intracerebrally with F98 cells 1 week later. Unvaccinated animals or those that received wild-type F98 cells as a vaccine had a survival time (mean +/- s.d.) of 22.3 +/- 1.5 days following tumor challenge versus 20.0 +/- 1.7 days for rats that had been vaccinated with F98/B7.1. Although we recognize that it might be possible to design more effective vaccination regimes, nevertheless, our data indicate that transfection of the B7.1 gene into the F98 rat glioma did not enhance its immunogenicity, and that other approaches will be required.

Animals↗
PubMed1983

[Immunogenic and non-immunogenic hyperthyroidism: attempts at a clinical differentiation].

In a retrospective study, 326 cases of thyroid hyperfunction but no scintigraphic demonstration of autonomous adenoma, were on the basis of certain primary and secondary criteria grouped as probably immunogenic or probably non-immunogenic hyperthyroid. Primary criteria were hormonal orbital signs and occurrence of thyroid antibodies. Secondary criteria concerned age, presence or absence of goitre and nodular goitre, scintigraphically silent areas and iodine contamination in relation to the onset of the disease. There was a significant difference between immunogenic and non-immunogenic hyperthyroidism by these criteria. In non-immunogenic hyperthyroidism, it is probable that suddenly raised iodine intake plays an important role in the initiation of hyperthyroid metabolic states. This was demonstrable in 82% of these patients, while in those with probably immunogenic hyperthyroidism iodine contamination (at 16%) seemed to be of less significance.

Age Factors↗
PubMed1999

Effect of virulence on immunogenicity of single and double vaccinia virus recombinants expressing differently immunogenic antigens: antibody-response inhibition induced by immunization with a mixture of recombinants differing in virulence.

It has been shown recently that the residual virulence of vaccinia virus (VV) is an important factor that influences the outcome of immunization with VV recombinants. This study focused on the correlation of the residual virulence of several VV recombinants with antibody responses against the strongly immunogenic extrinsic glycoprotein E of varicella-zoster virus and the weakly immunogenic extrinsic protein preS2-S of hepatitis B virus and against VV proteins, with mice used as a model organism. Furthermore, the effects of mixing different recombinants on the antibody response were studied. The results obtained indicated that: (i) the antibody response depended on the residual virulence of the recombinants, more so in the case of the weakly immunogenic protein; (ii) the residual virulence, the growth rate of the VV recombinants in extraneural tissues and the immunogenicity were associated features; (iii) immunization with mixtures of two differently virulent recombinants or with unequal amounts of two similarly virulent recombinants sometimes led to the suppression of antibody response. The appearance of this suppression was dependent on three factors: the residual virulence of the recombinants, the immunogenicity of the extrinsic proteins and the ratio of the recombinants in the mixtures. Thus, the data obtained demonstrate that there are various limitations to the use of replicating VV recombinants for immunization purposes.

Animals↗
PubMedDate not supplied

Immunogenic neoplastic clones derived in vitro from an originally non-immunogenic BALB/c fibrosarcoma.

A non-immunogenic fibrosarcoma (SDC2), obtained by spontaneous neoplastic transformation of BALB/c fibroblasts cultured within a diffusion chamber kept in the peritoneal cavity of (BALB/c x C3Hf)F1 mice, was maintained in tissue culture for 10 passages. Three different clones were then derived from the in vitro neoplastic population. Each of the clones, the original in vivo tumor, and its in vitro line taken at the 10th passage (before cloning) were tested for the presence of individual tumor-associated tramsplantation antigens (TATA) by in vivo growth and excision assay. Contrary to the original SDC2 neoplasm, its in vitro line and 2 out of 3 clones (CL1-SDC2 and CL3-SDC2) were immunogenic, whereas the other clone (CL6-SDC2) displayed no immunogenicity. In addition, CL1-SDC2 and CL3-SDC2 were able to induce a reciprocal cross-protection in in vivo transplantation tests, thus showing common TATA; no cross-reactions were found between these clones and 2 other chemically-induced immunogenic sarcomas. The results suggest an antigenic heterogeneity in the original population of the nonimmunogenic SDC2 sarcoma, with the presence of antigenic but sub-immunogenic neoplastic cells.

Animals↗
PubMed1992

Antibody responses to non-immunogenic synthetic peptides induced by co-immunization with immunogenic peptides.

Chimeric peptides comprising B- and T-helper cell epitopes from the proteins of infectious agents represent immunogens with potential for use as new vaccines. However, it has become clear that the orientation of the epitopes, the presence of spacer residues and the number of copies of the epitopes influence the specificity, levels and affinity of the antibody produced following immunization with such constructs. Furthermore, the response to peptides is under genetic control leading to major histocompatibility complex (MHC)-linked non-responsiveness. In this study, we have investigated the potential of co-immunization of immunogenic peptides (to provide T-cell help) with non-immunogenic peptides (representing B-cell epitopes) to overcome the non-response to the latter. For this purpose, we have employed peptides representing T- and B-cell epitopes derived from the sequences of the fusion and haemagglutinin glycoproteins of measles virus. The results obtained show that simple co-immunization of a B-cell epitope with a T-cell epitope results in the production of antibody to the B-cell epitope without the requirement for covalent linkage of the two peptides. This approach could thus be used to overcome the problem of poor immunogenicity of peptides and will be of potential value in the design of immunization strategies using synthetic immunogens.

Animals↗
PubMed1983

Demonstration of immunogenicity with the poorly immunogenic B16 melanoma.

Animal tumors of spontaneous origin have consistently been found to be less immunogenic than are tumors induced by chemical carcinogens or oncogenic viruses. Spontaneous tumors rarely demonstrate significant immunogenicity in classical transplantation rejection tests. This study demonstrates a novel approach to the question of tumor immunogenicity using viable tumor cells in diffusion chambers. Classical transplantation rejection was induced to the poorly immunogenic, spontaneous B16 murine melanoma by implantation of diffusion chambers containing viable B16 melanoma tumor cells. Implantation of B16 chambers i.p. for at least 4 weeks induced specific, long-term resistance to subsequent live B16 tumor cell challenge. In contrast, immunization with irradiated tumor cells for the same time interval resulted in a delay of tumor growth but had no effect on survival. These studies demonstrate the possibility that a significant anti-tumor immune response against the B16 melanoma may be induced without the presence and negative regulatory influences of a progressively growing B16 tumor. In addition, the diffusion chamber sensitization technique may detect the antigenicity of some tumors which are not detectable by classical transplantation rejection tests. Thus, the diffusion chamber technique provides another avenue for testing the immunogenicity of tumors, especially those of spontaneous origin.

Animals↗
PubMed1980

Distribution of immunogenic cells after painting with the contact sensitizers fluorescein isothiocyanate and oxazolone. Different sensitizers form immunogenic complexes with different cell populations.

The distribution of fluorescent cells in the draining lymph nodes of mice painted with the contact sensitizing agent fluorescein isothiocyanate (FITC) was investigated using a fluorescence-activated cell sorter. Up to 30% of the cells were fluorescent after 18 h and this decreased thereafter becoming undetectable after 4-5 days. Most of the fluorescent cells were morphologically lymphocytes, theta - ve and adherent to nylon wool. Immunogenicity of these cells was tested by injecting them into the footpads of normal mice and measuring contact sensitivity after 6 days. This was restricted to large cells which represented less than 5% of the white cell population and nearly all of which became fluorescent after skin painting. The large fluorescent cells were a mixture of monocytes and lymphocytes. Most of the lymphocytes had surface immunoglobulin. The immunogenicity was reduced by nylon filtration but was not affected by silica and anti-theta. These results showed that the immunogenicity is not associated with T cells. In contrast, similar immunogenic activity in the draining lymph nodes of mice painted with oxazolone is associated with T cells. The results therefore showed that different sensitizers form immunogenic complexes with different cell populations, perhaps in this case becuase of the different water solubilities of FITC and oxazolone. They also suggested that this may cause important differences in antigen presentation, for example in their association with different MHC products.

Animals↗
PubMed1995

Safety and immunogenicity of a gp120-depleted, inactivated HIV-1 immunogen: results of a double-blind, adjuvant controlled trial.

We report the safety and immunogenicity results of a double-blind adjuvant controlled trial of the human immunodeficiency virus type 1 (HIV-1) immunogen. Healthy, asymptomatic HIV-1-seropositive individuals received either three 100 microgram doses of the inactivated HIV-1 antigen in incomplete Freund's adjuvant (IFA) or three doses of IFA alone. The results of this study show that this HIV-1 immunogen is safe, with mild and transient adverse events. No difference in the number or type of adverse events was noted between the treatment groups. Rises in HIV-1-specific humoral and cell-mediated immune (CMI) responses were also noted, favoring the HIV-1 immunogen-treated group. The results of this study confirm and extend the safety and immunogenicity profile of this HIV-1 immunotherapeutic agent. The observation that this treatment can augment HIV-1-specific CMI is encouraging because this immunological marker may represent a key surrogate end point in HIV-1 infection and disease.

AIDS Vaccines↗
PubMed1996

Diverse manifestations of tumorigenicity and immunogenicity displayed by the poorly immunogenic B16-BL6 melanoma transduced with cytokine genes.

We evaluated the in vivo response to the poorly immunogenic B16-BL6 (BL6) murine melanoma genetically altered to secrete interleukin-2 (IL-2), IL-4, interferon gamma (IFN gamma) and granulocyte/macrophage-colony-stimulating factor (GM-CSF). Three parameters were evaluated: (1) tumorigenicity, (2) vaccination of naive animals, and (3) assessment of antitumor reactivity of T cells derived from tumor-draining lymph nodes (TDLN). Secretion of IL-2 abrogated the tumorigenicity of BL6, while IFN gamma and IL-4 partially reduced tumorigenicity, and GM-CSF had no effect. Protective immunity to wild-type tumor challenge could not be achieved by vaccination with irradiated cytokine-secreting tumors, although IL-2 and IL-4 secretion appeared to retard the growth of the challenge inoculum significantly. An alternative method to evaluate the immunogenicity of the cytokine-secreting tumors was to measure the ability of T cells obtained from TDLN to mediate regression of wild-type tumor in adoptive immunotherapy. Neither IL-2 nor IFN gamma secretion resulted in the induction of immune T cells. By contrast, GM-CSF and IL-4 secretion were found to induce immune T cells in the TDLN with GM-CSF being superior to IL-4. The combined secretion of GM-CSF and IL-4 did not lead to enhanced induction of immune T cells. GM-CSF secretion was found to upregulate B7-1 expression in TDLN, consistent with an increase in the population of antigen-presenting cells. These studies demonstrated that reduced tumorigenicity by cytokine secretion did not correlate with increased immunogenicity. With the cytokines examined, there was limited capability of developing protective immunity against the BL6 tumor. Nevertheless, GM-CSF and IL-4 secretion significantly enhanced T cell immune reactivity to the poorly immunogenic BL6 tumor.

Animals↗
PubMed1987

In vitro B-lymphocyte antigen priming against both non-immunogenic and immunogenic molecules requiring low amounts of antigen and applicable in hybridoma technology.

A method to efficiently antigen-prime B-lymphocytes with low amounts (less than 1 microgram/10(8) cells) of either immunogenic or non-immunogenic molecules is described. Keyhole limpet hemocyanin (KLH) and histone were used as prototypes for strongly immunogenic and for phylogenetically conserved non-immunogenic epitopes, respectively. Several modifications of previously reported methods were applied to the system and resulted in the requirement of antigen amounts sufficiently low to be obtainable by elution of proteins from electrophoretic gels. Antigen priming against highly purified antigen preparations is thereby feasible even when purified material cannot be obtained by conventional biochemical procedures. The amount of T- and B-lymphocytes and interleukin-2 production was estimated under various conditions during the priming procedure, and those optimal for generation of a high number of antigen-specific B-lymphocytes determined. In vitro antigen-primed B-lymphocytes were immortalized by conventional hybridoma technology. By fusion of lymphoid cells with myeloma cells at each day during the antigen-priming period, the optimal day of fusion to generate antigen-specific hybridomas was determined. Further, in 12 experiments with different antigens, 11 monoclonal antibodies to histones H3 and H4, two to the murine glucose transporter, 17 to trinitrophenyl-sheep red blood cells, and 20 to KLH were obtained. All specific hybridomas produced IgMs, as the antigen-priming period could not be extended for more than 9-10 days, whereafter a rapid decay in B-lymphocytes occurred.

Animals↗
PubMed1996

Retrovirus-mediated gene transfer of B7-1 and MHC class II converts a poorly immunogenic neuroblastoma into a highly immunogenic one.

The T cell co-stimulatory molecule B7-1 was transduced into a poorly immunogenic murine neuroblastoma cell line (Neuro-2a, N-2a) alone or in combination with MHC class II genes to test the ability of these genes to stimulate antitumor immunity. N-2a cells transduced with B7-1 exhibited reduced tumorigenicity, whereas N-2a cells overexpressing both MHC class II (syngeneic, I-Ak) and B7-1 totally abrogated tumorigenicity. Rejection of I-Ak/B7-1 cells was dependent on both CD4+ and CD8+ T cells. The ability of both vaccines to induce protection against parental N-2a was temporally dependent on the time of secondary N-2a challenge. To investigate the immunity generated by N-2a/B7-1 and N-2a/I-Ak/B7-1 vaccines, we tested the ability of these modified cells to stimulate in vitro the proliferation of syngeneic splenocytes from naive mice. A significant increase in splenocyte proliferation was observed with N-2a/I-Ak/B7-1 cells compared to N-2a cells. We also determined that vaccination with N-2a/I-Ak/B7-1 cells was able to generate cytotoxic T cell responses to unmodified N-2a cells. The introduction of B7-1 and I-Ak into N-2a was able to convert a poorly immunogenic tumor to a highly immunogenic one; however, mice bearing large established unmodified tumors had little response to vaccination with N-2a/I-Ak/B7-1 cells. Our results emphasize the importance of tumor immunogenicity in the treatment of established tumors with MHC class II/B7-1 tumor cell vaccines.

Animals↗
PubMed1989

Enhanced immunogenicity of a T cell immunogenic peptide by modifications of its N and C termini.

The modification of the terminal ionizable charges of an immunogenic peptide, HEL (46-61), was found to greatly increase the immunogenicity of the peptide. The modified peptide had 100- to 1000-fold enhanced activity in both in vitro and in vivo T cell assays. The mechanism of the enhancement was investigated by determining the binding affinities to I-Ak as well as circular dichroism (CD) studies. The native and enhanced peptides had indistinguishable binding affinities, as well as similar kinetics. The CD studies revealed that in aqueous solution, neither peptide had any detectable helicity; however, the addition of trifluoroethanol did result in significant helicity; with the two peptides being indistinguishable. These same modifications were also shown to enhance other immunogenic peptides if they contained a basic carboxy-terminal amino acid residue. Thus, by modifying the termini of T cell epitopes, their immunogenicity can be dramatically increased, but the molecular basis for this enhancement is still unclear.

Amino Acid Sequence↗