Biomedical subjects

D Gerlier

Publications and source records attributed to D Gerlier.

At least 55 records · Page 3Linked to original sources

PubMed1993

Can one predict antigenic peptides for MHC class I-restricted cytotoxic T lymphocytes useful for vaccination?

The cytotoxic T-lymphocyte (CTL) response can be crucial for efficient immunological control of intracellular pathogens and the MHC class I-restricted CTL have a major role to play in this process. They recognize complexes associating antigen-derived peptides with MHC class I molecules expressed on infected target cells. The characterization of these antigenic peptides is thus a key issue for developing vaccines efficient in inducing specific CTL. Recently, by sequencing the whole set of self-peptides eluted from a given MHC class I molecule, Falk and colleagues have found that they have a homogeneous 8-10 residue length and contain allele-specific peptidic motifs with two conservative dominant anchor residues. The existence of consensus motifs opens the way for a strategy to predict the MHC class I-restricted T-cell epitopes and here we discuss such an approach using hen egg lysozyme (HEL) as an antigenic model. Two HEL peptides corresponding to allele-specific motifs were found, HEL(49-56) and HEL(70-78) peptides, which can associate with MHC class I H-2Kb and H-2Db molecules, respectively. The HEL peptide HEL(70-78) was found to be able to induce HEL-specific CTL in H-2b mice also. Moreover, using an empiricial approach, we have also characterized the N-terminal HEL(1-17) peptide as an immunodominant antigenic peptide in the H-2k haplotype. This peptide presented by H-2Kk molecules neither contained the corresponding allele-specific binding motif nor fitted the expected 8-10 residue length.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1993

Measles virus haemagglutinin induces down-regulation of gp57/67, a molecule involved in virus binding.

A surface glycoprotein (gp57/67) was previously shown to be involved in measles virus (MV) binding and characterized in our laboratory. Here, we described down-regulation of cell surface gp57/67 after infection with MV. This effect is specific for MV since cells infected with canine distemper virus, closely related to MV, did not down-regulate gp57/67. The decrease in cell surface gp57/67 correlated with expression of MV glycoproteins and more particularly with the expression of MV haemagglutinin (MV-H). Indeed, expression of MV-H after infection with a vaccinia virus recombinant coding for MV-H was necessary and sufficient to induce down-regulation of gp57/67. Kinetics of cell surface expression of MV-H and gp57/67 showed that the degree of down-regulation was correlated with the amount of MV-H expressed by infected cells. Experiments using antibody-prelabelled gp57/67 and indirect immunofluorescence microscopy allowed us to follow the fate of gp57/67 and showed that down-regulation was occurring by rapid internalization of gp57/67 from the cell surface. These results provide additional evidence that the gp57/67 molecule is closely associated with the pathway of MV infection and also reveal a phenomenon which may be related to viral pathogenesis and persistence.

Biological Transport↗

PubMed1993

Human membrane cofactor protein (CD46) acts as a cellular receptor for measles virus.

A monoclonal antibody (MCI20.6) which inhibited measles virus (MV) binding to host cells was previously used to characterize a 57- to 67-kDa cell surface glycoprotein as a potential MV receptor. In the present work, this glycoprotein (gp57/67) was immunopurified, and N-terminal amino acid sequencing identified it as human membrane cofactor protein (CD46), a member of the regulators of complement activation gene cluster. Transfection of nonpermissive murine cells with a recombinant expression vector containing CD46 cDNA conferred three major properties expected of cells permissive to MV infection. First, expression of CD46 enabled MV to bind to murine cells. Second, the CD46-expressing murine cells were able to undergo cell-cell fusion when both MV hemagglutinin and MV fusion glycoproteins were expressed after infection with a vaccinia virus recombinant encoding both MV glycoproteins. Third, M12.CD46 murine B cells were able to support MV replication, as shown by production of infectious virus and by cell biosynthesis of viral hemagglutinin after metabolic labeling of infected cells with [35S]methionine. These results show that the human CD46 molecule serves as an MV receptor allowing virus-cell binding, fusion, and viral replication and open new perspectives in the study of MV pathogenesis.

Amino Acid Sequence↗

PubMed1993

Inhibition by chloroquine of the class II major histocompatibility complex-restricted presentation of endogenous antigens varies according to the cellular origin of the antigen-presenting cells, the nature of the T-cell epitope, and the responding T cell.

Chloroquine treatment of antigen-presenting cells (APC) was explored as a tool to investigate the processing pathway for major histocompatibility complex (MHC) class II-restricted presentation of the endogenous secreted hen egg lysozyme (HEL) and transmembrane measles virus haemagglutinin (HA). A 72-hr pretreatment of the APC with 25 microM chloroquine blocked the presentation of the HEL(52-61) T-cell epitope generated from endogenous HEL to the I-Ak-restricted 3A9 T-cell hybridoma by MHC class II-transfected L cells expressing the invariant chain (Ii). The presentation of exogenously added HEL peptides was not affected. Under the same conditions, no inhibition of the presentation of HEL(106-116) to the I-Ed-restricted G28 high-avidity T-cell hybridoma, nor of HA when synthesized by L cells, was observed. When B-lymphoid APC were used, inhibition was observed in every case with a low number of B APC pretreated for 48 hr with chloroquine prior to the T-cell stimulation test. Moreover, addition of chloroquine to untreated B APC during the T-cell stimulation assay was sufficient to inhibit completely the presentation of HEL(106-116) to the B10.D24.42 low avidity T-cell hybridoma. Altogether these studies suggest that an apparent resistance of endogenous Ag presentation to chloroquine inhibition may not necessarily indicate the existence of a non-endosomal pathway but may be due to the nature of the T-cell epitope, to the use of 'non-professional' APC such as L cells, to the use of T cells of high avidity, and to high amounts of pre-existing MHC class II-peptide complexes expressed by the APC. We demonstrate here that, at least in conventional APC such as B cells, class II-restricted presentation of both endogenous secreted HEL and transmembrane HA involves an endosomal pathway.

Animals↗

PubMed1992

High efficiency of endogenous antigen presentation by MHC class II molecules.

MHC class II molecules are involved in the presentation of both exogenous and endogenous antigens to CD4 T cells. Using the trans-membrane hemagglutinin (HA) from measles virus and the secreted hen egg lysozyme (HEL) as antigen models, we have compared the efficiency of MHC class II presentation by naive antigen presenting cells (APCs) pulsed with exogenous antigen with that of their transfected counterparts synthesizing endogenous antigen. B cells expressing even a very low amount of trans-membrane HA were found to present endogenous HA to I-Ed restricted T cell hybridomas with a high efficiency whereas their naive counterparts required to be pulsed with a comparatively high amount of exogenous HA. Similarly, MHC class II presentation of endogenous secreted HEL was found to be much more efficient when compared with that of exogenous HEL. Biochemical studies did not reveal any enhanced intracellular degradation of endogenous HEL. As expected, HEL was released in the surrounding medium within < 1 h. MHC class II presentation of endogenous HEL could not be explained by re-uptake by bystander APCs of HEL secreted in the surrounding medium. No sensitization of naive APCs could be observed either when co-cultured with HEL secreting cells or when cultured for 10 days with a sub-threshold amount of exogenous HEL. At the cell surface, I-Ed molecules immunoprecipitated from HEL secreting cells were found to be slightly enriched in SDS-resistant forms. These data raised the question of how peptides derived from endogenous transmembrane and secreted antigens can so efficiently reach an MHC class II loading compartment.

Animals↗

PubMed1992

A monoclonal antibody recognizes a human cell surface glycoprotein involved in measles virus binding.

Measles virus (MV) has a very limited host range, humans being the only natural reservoir of the virus. This restriction may be due to the absence of an MV receptor on the surface of non-primate cells. We have studied the MV-binding ability of several cell lines and attempted to characterize the receptor by studying the binding of 35S-labelled MV and by a rosette formation technique. We confirmed that all the human cell lines examined (HeLa, Raji and Jurkat) bound MV and that the murine cell lines (BW and L) did not. The glycoprotein nature of the receptor activity was demonstrated by the fact that it could be removed from the cell membrane using proteolytic enzymes and by its failure to be re-expressed in the presence of a protein synthesis inhibitor or an N-glycosylation inhibitor. A monoclonal antibody isolated after immunization of mice with Raji cells specifically inhibited MV binding and infection of human cells, and recognized human and simian but not murine cells. Depending on the cell line (HeLa, Raji, Jurkat or Vero), this antibody immunoprecipitated one or two glycoproteins with apparent M(r)s of 57K and/or 67K from human and simian cells, but not from murine cells.

Animals↗

PubMed1991

Cytosolic targeting of hen egg lysozyme gives rise to a short-lived protein presented by class I but not class II major histocompatibility complex molecules.

A way to study the role of intracellular trafficking of an antigen in its presentation to T cells is to target the antigen to various cell compartments of the antigen-presenting cells (APC) and compare the nature of the complexes associating major histocompatibility complex (MHC) molecules and antigenic peptides, expressed on the cell surface. MHC class I+ and MHC class II+ mouse L fibroblasts secreting hen egg lysozyme (HELs cells) or expressing HEL in their cytosol (HELc cells) were obtained after transfection with HEL cDNA and signal sequence-deleted HEL cDNA, respectively. HEL was evidenced in both HELs- and HELc-transfected cells and the former type of transfectant secreted a large amount of HEL. However, HEL produced in the cytosol exhibited a short half-life of less than 5 min. HEL-derived peptides could not be shown biochemically either in HELc- nor in HELs-transfected cells. We then studied the capacity of these cells to present HEL to HEL-specific class I- and class II-restricted T cells. Both cell types could be recognized by the HEL-specific MHC class I-restricted CTL clones. In contrast, MHC class II-HEL peptide complexes, recognized by HEL-specific helper T cell hybridomas, could be detected on MHC class II+ HELs- but not HELc-transfected cells. In vivo experiments showed, however, that HELc-transfected cells could provide host APC with HELc-derived peptides able to associate with MHC class II molecules. This was inferred from the capacity of MHC class II-HELc-transfected cells, unable by themselves to elicit any anti-HEL antibody response, to prime syngeneic and allogeneic mice against HEL. The priming was revealed by the induction of an antibody response after a boost with an amount of HEL unable itself to elicit an antibody response.

Amino Acid Sequence↗

PubMed1991

Enhancement of in vivo and in vitro T cell response against measles virus haemagglutinin after its incorporation into liposomes: effect of the phospholipid composition.

Artificial phospholipid bilayer vesicles were tested for their capacity to enhance the priming and the restimulation of mouse T cells against the haemagglutinin (H) glycoprotein of the measles virus in vivo and in vitro. H glycoprotein was purified and incorporated into liposomes made of cholesterol, dicetylphosphate and dilauroylphosphatidylcholine (DLPC) or distearoylphosphatidylcholine (DSPC). H in DLPC or DSPC-liposomes was found to be a potent in vivo stimulator of lymph node T cells harvested from mice immunized with measles virus, whereas H glycoprotein in free form did not elicit any proliferative T cell response. When used to immunize naive mice, only H in DSPC-liposomes was able to prime T cells as evidenced by the capacity of lymph node cells to proliferate in the presence of H in liposomes or measles virus as secondary stimulating agents in vitro. H-specific T cell clones derived from animals immunized with H in DSPC-liposomes were able to recognize H glycoprotein both in free form and incorporated into liposomes in the presence of naive spleen cells as APC. However, compared with the liposome forms, 20-fold more H protein in free form was required to elicit a T cell clone response at a similar level. This liposome immune enhancing effect on the T cell clone recognition of H glycoprotein was also observed when peritoneal exudate cells were used as APC. These data demonstrate that the insertion of a membrane-derived antigen into artificial membranes may be a prerequisite for the priming and stimulation of specific T cells both in vivo and in vitro. In addition, the nature of the phospholipid used to build the liposomes appears to be a critical parameter.

Animals↗

PubMed1991

Correlation between invariant chain expression level and capability to present antigen to MHC class II-restricted T cells.

In this study we investigated the role of the invariant chain (li) in the presentation of hen egg lysozyme (HEL) and measles virus hemagglutinin (HA) antigens to MHC class II-restricted T hybridoma cells. Fibroblastic cells transfected with Ed or Ak genes, and supertransfected or not with the li gene, were used as antigen-presenting cells (APC). For every APC pair analysed, the amount of exogenous antigen needed to obtain a T-cell response was inversely correlated with the level of li expression. Exogenously provided HEL was efficiently presented by li-supertransfected APC at doses of 10 micrograms/ml or below. In contrast, non-li transfected fibroblastic cells, which express a low level of endogenous li, required at least 10 times more HEL to stimulate most of the T hybridoma cells. Analogous results were also obtained using exogenous HA. Finally, two different experiments suggest that basal li expressed in fibroblastic cells is involved in the presentation of exogenous antigen. In the first one, we showed that li/class II ratio was increased in high-density grown fibroblastic cells and that this increase correlates with the ability of the cells to present exogenous antigen. In the second, treating high-density grown cells with an antisense li oligodeoxynucleotide could impair their ability to present exogenous HEL. We also examined the presentation of endogenously-synthesized HEL or HA after introduction of the antigen into the biosynthetic pathway of the APC by transfection of HEL and HA cDNAs. There was no apparent difference in the capability of high density grown fibroblastic cells, transfected or not with li gene, to present endogenous HEL or HA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Generation of hen egg lysozyme-specific and major histocompatibility complex class I-restricted cytolytic T lymphocytes: recognition of cytosolic and secreted antigen expressed by transfected cells.

Syngeneic cells exogenously supplied with hen egg lysozyme (HEL) or endogenously synthesizing HEL were used as antigen-presenting cells to induce major histocompatibility complex class I-restricted cytotoxic T lymphocytes (CTL). Immunization of C57BL/6 mice followed by repeated stimulation of their splenocytes in vitro with trypsinized HEL peptides led to the generation of CTL lines specific for trypsinized HEL peptides and restricted by H-2K. Immunization of C3H mice with a mixture of soluble native HEL and irradiated syngeneic spleen cells followed by in vitro stimulation of immune spleen cells with soluble HEL could in a few cases result in HEL-specific CTL able to kill syngeneic transfectant L cells secreting HEL (HELs) or expressing cytosol-targeted HEL (HELc). The use of HELs or HELc transfectant L cells as in vivo and in vitro immunogens was a potent way for eliciting HEL-specific polyclonal CTL. These CTL and two CD8+ clones were found to be H-2K restricted and specific for the 1-17 N-terminal HEL peptide. In addition, the anti-HEL CTL could also exhibit a significant cross-reactivity against unsensitized and HEL-untransfected targets expressing the K restriction element. This cross-reactivity was likely due to recognition of unidentified HEL mimicking peptides (self-derived?) presented by the MHC class I (H-2K or H-2K) molecule used as the restriction element for the specific recognition of HEL. The CTL raised after immunization with HELs or HELc transfectant cells were found to recognize both the HELs and HELc transfectant cells even though HEL was not detected in the latter after a 2- or 5-min radiolabeling pulse. Recognition of both HELs and HELc transfectant cells by a given CTL clone suggests that HEL subjected to two separate processing pathways, each depending on the initial subcellular localization, can ensure the generation of similar MHC class I peptide complexes.

Animals↗

PubMed1989

Antigen processing--from cell biology to molecular interactions.

Antigen presentation is now a central theme in molecular cell biology. A recent meeting focused on the developments in the field and their implications for future manipulation of the immune system. The following report was written from a round-table discussion involving a number of participants'.

Antigen-Presenting Cells↗

PubMed1988

Human T-cell leukemia virus type I-induced proliferation of human thymocytes requires the presence of a comitogen.

HTLV-I has recently been shown to be a direct activator of resting human peripheral T cells. In order to determine the susceptibility of T-cell precursors to HTLV-I mitogenic activity we have exposed human thymic T cells to uv-inactivated HTLV-I. Unlike mature T cells, thymocytes were not directly susceptible to HTLV-I-induced activation although agglutination of cells did occur after exposure to HTLV-I alone. However, in the presence of another stimulus, phyto-hemagglutinin or anti-CD3 monoclonal antibodies and accessory cells, thymocytes proliferated when exposed to HTLV-I. Concanavalin A did not induce HTLV-I comitogenic activity. HTLV-I-induced thymocyte proliferation was enhanced by autologous or heterologous accessory cells. This proliferation was shown to be mediated by the interleukin-2/interleukin-2 receptor pathway. Simultaneous stimulation by HTLV-I and nonmitogenic doses of phytohemagglutinin were required both for the production of interleukin-2 and for the expression of the interleukin-2 receptor. These data demonstrated functional differences between peripheral T cells and thymocytes.

Adult↗

PubMed1988

Humoral immune response elicited in rats by measles viral membrane antigens presented in liposomes and ISCOMs.

The immunogenicity of measles virus glycoproteins presented associated to liposomes or ISCOMs was compared with that of whole virus and solubilized membrane proteins in W/Fu rats. The rats were immunized three times at ten-day intervals with syngeneic peritoneal exudate cells fed in vitro with the various antigen preparations. A strong and persisting antibody response with haemagglutinin inhibitory and neutralization activity was observed in rats immunized with liposomes, ISCOMs, or virus. The responses were very similar despite the lower dose of protein received by rats immunized with ISCOMs (1 microgram protein) or with liposomes (20 micrograms protein). By contrast, injection of peritoneal exudate cells previously fed in vitro with soluble H and F glycoproteins resulted in only a poor and transient response. The sera from rats immunized with virus, liposomes or ISCOMs contained antibodies immunoprecipitating mainly H and F glycoproteins. Despite a strong enrichment in F polypeptides during the preparation of ISCOMs, they induced an equal anti-H and anti-F antibody response.

Adjuvants, Immunologic↗

PubMed1988

Haemagglutinin of measles virus: purification and storage with preservation of biological and immunological properties.

Measles virus envelope haemagglutinin (H) was purified rapidly with Triton X-100-solubilized virions by a two-step anion-exchange chromatography using fast protein liquid chromatography. The purity of the glycoprotein in its dimeric form was demonstrated by SDS-PAGE followed by silver staining or autoradiography. The purified H glycoprotein was further freed from contaminating detergent by dialysis of octylglucoside detergent. This purification procedure, together with subsequent lyophilization and storage at -70 degrees C of the H glycoprotein which was incorporated into phospholipid vesicles allowed the full preservation of its haemagglutinating activity, its reactivity with a monoclonal anti-H antibody that recognized a conformational epitope and its capacity to elicit anti-H antibodies with haemagglutination-inhibiting and neutralizing activities.

Animals↗

PubMed1987

Regulation of the expression on mouse T lymphocytes of the epitope identified by monoclonal antibody 3A35.

Monoclonal antibody 3A35 (MA 3A35) has previously been shown to be an activation marker of macrophages and T lymphocytes. It immunoprecipitated from macrophages a 200-kDa molecule belonging to the T200 family and from T cells a 85-kDa antigen. In the present work, the factors controlling the expression of the epitope identified by MA 3A35 on polyclonal activated T cells and T-cell clones, as well as the ability of 3A35 alone or together with complement to interfere with T-cell functions, were investigated. Corticoresistant thymocytes unreactive with MA 3A35 became fully reactive after 2 days of in vitro stimulation by PMA and IL-2 and the level of reactivity per cell declined to a low level thereafter. In helper and cytolytic T-cell clones, the expression of the epitope defined by MA 3A35 was also maximal soon after antigenic stimulation then declined. In helper-T-cell clones, the epitope remained detectable during the entire culture period, whereas in cytolytic clones its expression was markedly reduced at the end of the culture. The lineage of cytotoxic T lymphocytes (CTL) as studied in a bulk culture of spleen cells primed in vivo against a syngeneic tumor exhibited similar regulation by antigenic stimulation. The CTL precursors were resistant to lysis by MA 3A35 plus complement; after 3 days of culture with the stimulatory antigen, they became highly sensitive but their sensitivity then diminished and mature CTL were completely resistant. MA 3A35 plus complement also killed the activated T cells which responded to macrophage-presented antigens and were thought to be mainly Lyt-1+. Therefore, the epitope identified by MA 3A35 was expressed predominantly at an early stage of T-cell activation. At a late stage, it persisted almost exclusively on helper and Lyt-1+ cells. In addition, MA 3A35 plus complement lysed NK cells, AK cells, and their precursors present in normal spleen. In the absence of complement, MA 3A35 had no detectable effect on T-cell functions.

Animals↗

PubMed1987

A new epitope of the T200 molecule family defined by the 3A35 monoclonal antibody and expressed by macrophages and activated T lymphocytes.

A monoclonal antibody (mAb), 3A35, produced against mouse macrophages (M phi) was found to react against certain activated T cells. This mAb, a rat IgM, resulted from a cell fusion between a mouse plasmacytoma and rat lymphocytes immunized against mouse M phi. It bound more avidly to activated than to resident M phi. It did not react against B cells and resting T lymphocytes but recognized certain dividing T cells like EL4 lymphoma, concanavalin A-activated and interleukin 2-expanded spleen cells, and helper T cell hybridomas. By contrast, other T lymphocyte-derived cell lines such as YAC-1 and CTLL2 were unreactive. No clear relationship was found between the binding of 3A35 to cells and the expression of L3T4 and Lyt-2 antigens. The specific stimulation of T cell clones with antigen rapidly induced a strong reactivity with 3A35 mAb which declined thereafter to a low (helper clones) or non-reactivity (cytotoxic clones) after 10 days of culture. Immunoprecipitation experiments, performed with M phi derived from bone marrow cell cultures, surface iodinated with 125I or metabolically labeled with [35S]methionine, showed that 3A35 bound to a 200-kDa molecule, shifting to 175 kDa under reducing conditions. In peritoneal M phi activated in vivo, in addition to the 175-kDa band, new bands migrating at 140, 120 and 85 kDa were identified by 3A35 and could be absorbed on a commercial anti-T200 mAb bound to Sepharose beads. After strengthening the cell binding of 3A35 to EL4 lymphoma cells by a cross-linking agent, only a 85-kDa molecule was immunoprecipitated. Thus, 3A35 identifies a new epitope of the T200 molecule family which is expressed on M phi and activated T cells.

Animals↗

PubMed1987

Impairment of immunogenicity by antigen presentation in liposomes made from dimyristoylphosphatidylethanolamine linked to the secretion of prostaglandins by macrophages.

The induction of antibody response in syngeneic rats by the Gross virus cell surface antigen (GCSAa) was dependent on the presentation of GCSAa into liposomes made from distearoylphosphatidylcholine (DSPC). GCSAa liposomes made from dimyristoylphosphatidylethanolamine (DMPE) were nonimmunogenic, even when used as anamnestic immunogens. Spleen cells, from rats twice immunized with GCSAa-DSPC-liposomes and used to transfer the anti-GCSAa immune response into naive recipients after a tertiary immunostimulation in vitro in the presence of naive peritoneal exudate cells (PEC), responded to soluble GCSAa only after irradiation at 500 rds and to GCSAa-DMPE-liposomes only when indomethacin was added during the in vitro stimulation. The preincubation of these cells with empty DMPE liposomes or the addition of supernatant from PEC fed with DMPE liposomes abrogated the response to GCSAa-DSPC liposomes. Using a specific radioimmunoassay, prostaglandin E2 was demonstrated to be produced by PEC when fed with DMPE liposomes, and not when fed with DSPC liposomes. This prostaglandin E2 secretion by PEC induced by DMPE liposomes was inhibited by indomethacin.

Animals↗

PubMed1987

In vitro cellular immune response to measles viral glycoproteins: role of the antigen vector.

The capacity of measles virus and haemagglutinin (HA) and fusion (F) glycoproteins, presented either as soluble antigens, associated with liposomes or as Iscoms, to induce an in vitro primary and anamnestic cellular response was studied in syngeneic W/Fu rats using the MTT colorimetric assay. A primary cellular response was observed when the virus, HA + F liposomes or HA + F Iscoms were used as immunogens, but not when soluble HA + F glycoproteins were used. The irradiation of the naïve spleen cells at 500 rads allowed the generation of a primary response with the soluble antigens. All these primary responses were low, of similar intensity and dose-dependent. The responses were stronger after the stimulation of spleen cells from seropositive immune rats with virus, HA + F liposomes or HA + F Iscoms, whereas they were moderate after stimulation with soluble HA + F. In addition, far less antigenic material was required and the use of a vehicle for HA + F (liposomes, Iscoms) dramatically lowered the threshold of the sensitivity to the antigens. The immunization of rats with soluble HA + F glycoproteins resulted in the anergy of their spleen cells even to virus, HA + F liposomes or HA + F Iscoms. Again, irradiation of these cells could restore their ability to elicit a primary response to any type of HA + F immunogens. Using the lysosomotropic Leu-0-Met agent, all the cellular responses were found to be accessory cells dependent, the responses being restored after supplementation with 10% peritoneal exudate cells from naïve rats. These treatments did not break the immunosuppression induced by soluble HA + F glycoproteins. The uptake of the various immunogens by the murine macrophage cell line J774-1 was also studied using radioactively labelled virus and HA + F glycoproteins. The uptake of soluble HA + F was limited to 10-15%, whereas that of the other immunogens was almost complete. The data reported indicate that the modification of the supramolecular architecture of HA + F glycoproteins by their presentation in liposomes or Iscoms could modulate their immunogenicity, both qualitatively and quantitatively. It could prevent the generation of a radiosensitive suppressive mechanism, increase the sensitivity to the antigen and the activation level of the responding cell population. Quantitative modifications are accessory cell dependent and initiated within the first hour of the stimulation.

Animals↗