[A median lumbar cutaneous fistula in a 3-year-old child].
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Child, Preschool↗
Biomedical subjects
H Zaghouani
Publications and source records attributed to H Zaghouani.
Neonatal exposure to antigen primes the immune system to develop responses in various lymphoid organs and promotes bystander regulation of diverse T cell specificities.
Neonatal exposure to Ag has always been considered suppressive for immunity. Recent investigations, however, indicated that the neonatal immune system could be guided to develop immunity. For instance, delivery of a proteolipid protein (PLP) peptide on Ig boosts the neonatal immune system to develop responses upon challenge with the PLP peptide later. Accordingly, mice given Ig-PLP at birth and challenged with the PLP peptide as adults developed proliferative T cells in the lymph node that produced IL-4 instead of the usual Th1 cytokines. However, the spleen was unresponsive unless IL-12 was provided. Herein, we wished to determine whether such a neonatal response is intrinsic to the PLP peptide or could develop with an unrelated myelin peptide as well as whether the T cell deviation is able to confer resistance to autoimmunity involving diverse T cell specificities. Accordingly, the amino acid sequence 87-99 of myelin basic protein was expressed on the same Ig backbone, and the resulting Ig-myelin basic protein chimera was tested for induction of neonatal immunity and protection against experimental allergic encephalomyelitis. Surprisingly, the results indicated that immunity developed in the lymph node and spleen, with deviation of T cells occurring in both organs. More striking, the splenic T cells produced IL-10 in addition to IL-4, providing an environment that facilitated bystander deviation of responses to unrelated epitopes and promoted protection against experimental allergic encephalomyelitis involving diverse T cell specificities. Thus, neonatal exposure to Ag can prime responses in various organs and sustain regulatory functions effective against diverse autoreactive T cells.
Animals↗
Neonatal immunity develops in a transgenic TCR transfer model and reveals a requirement for elevated cell input to achieve organ-specific responses.
In recent years, it has become clear that neonatal exposure to Ag induces rather than ablates T cell immunity. Moreover, rechallenge with the Ag at adult age can trigger secondary responses that are distinct in the lymph node vs the spleen. The question addressed in this report is whether organ-specific secondary responses occur as a result of the diversity of the T cell repertoire or could they arise with homogeneous TCR-transgenic T cells. To test this premise, we used the OVA-specific DO11.10 TCR-transgenic T cells and established a neonatal T cell transfer system suitable for these investigations. In this system, neonatal T cells transferred from 1-day-old DO11.10/SCID mice into newborn (1-day-old) BALB/c mice migrate to the host's spleen and maintain stable frequency. The newborn BALB/c hosts were then given Ig-OVA, an Ig molecule carrying the OVA peptide, and challenged with the OVA peptide in CFA at the age of 7 wk; then their secondary responses were analyzed. The findings show that the lymph node T cells were deviated and produced IL-4 instead of IFN-gamma and the splenic T cells, although unable to proliferate or produce IFN-gamma, secreted a significant level of IL-2. Supply of exogenous IL-12 during Ag stimulation restores both proliferation and IFN-gamma production by the splenic T cells. This restorable form of splenic unresponsiveness referred to as IFN-gamma-dependent anergy required a transfer of a high number of neonatal DO11.10/SCID T cells to develop. Thus, the frequency of neonatal T cell precursors rather than repertoire diversity exerts control on the development of organ-specific neonatal immunity.
Amino Acid Sequence↗
Neonatal exposure to antigen induces a defective CD40 ligand expression that undermines both IL-12 production by APC and IL-2 receptor up-regulation on splenic T cells and perpetuates IFN-gamma-dependent T cell anergy.
T cell deletion and/or inactivation were considered the leading mechanisms for neonatal tolerance. However, recent investigations have indicated that immunity develops at the neonatal stage but evolves to guide later T cell responses to display defective and/or biased effector functions. Although neonatal-induced T cell modulation provides a useful approach to suppress autoimmunity, the mechanism underlying the biased function of the T cells remains unclear. In prior studies, we found that exposure of newborn mice to Ig-PLP1, a chimera expressing the encephalitogenic proteolipid protein (PLP) sequence 139-151, induced deviated Th2 lymph node cells producing IL-4 instead of IL-2 and anergic splenic T cells that failed to proliferate or produce IFN-gamma yet secreted significant amounts of IL-2. However, if assisted with IFN-gamma or IL-12, these anergic splenic T cells regained full responsiveness. The consequence of such biased/defective T cells responses was protection of the mice against experimental allergic encephalomyelitis. In this study, investigations were performed to delineate the mechanism underlying the novel form of IFN-gamma-dependent splenic anergy. Our findings indicate that CD40 ligand expression on these splenic T cells is defective, leading to noneffective cooperation between T lymphocytes and APCs and a lack of IL-12 production. More striking, this cellular system revealed a requirement for IL-2R expression for CD40 ligand-initiated, IL-12-driven progression of T cells into IFN-gamma production.
Animals↗
Binding site for chitin oligosaccharides in the soybean plasma membrane.
Affinity cross-linking of the plasma membrane fraction to an (125)I-labeled chitin oligosaccharide led to the identification and characterization of an 85-kD, chitin binding protein in plasma membrane-enriched fractions from both suspension-cultured soybean cells and root tissue. Inhibition analysis indicated a binding preference for larger (i.e. degrees of polymerization = 8) N-acetylated chitin molecules with a 50% inhibition of initial activity value of approximately 50 nM. N-Acetyl-glucosamine and chitobiose showed no inhibitory effects at concentrations as high as 250 microM. It is noteworthy that the major lipo-chitin oligosaccharide Nod signal produced by Bradyrhizobium japonicum was also shown to be a competitive inhibitor of ligand binding. However, the binding site appeared to recognize the chitin portion of the Nod signal, and it is unlikely that this binding activity represents a specific Nod signal receptor. Chitooligosaccharide specificity for induction of medium alkalinization and the generation of reactive oxygen in suspension-cultured cells paralleled the binding activity. Taken together, the presence of the chitin binding protein in the plasma membrane fraction and the specificity and induction of a biological response upon ligand binding suggest a role for the protein as an initial response mechanism for chitin perception in soybean (Glycine max).
Binding Sites↗
Multi-modal antigen specific therapy for autoimmunity.
Peripheral tolerance, represents an attractive strategy to down-regulate previously activated T cells and suppress an ongoing disease. Herein, immunoglobulins (Igs) were used to deliver self and altered self peptides for efficient peptide presentation without costimulation to test for modulation of experimental allergic encephalomyelitis (EAE). Accordingly, the encephalitogenic proteolipid protein (PLP) sequence 139-151 (referred to as PLP1) and an altered form of PLP1 known as PLP-LR were genetically expressed on Igs and the resulting Ig-PLP1 and Ig-PLP-LR were tested for efficient presentation of the peptides and for amelioration of ongoing EAE. Evidence is presented indicating that Ig-PLP1 as well as Ig-PLP-LR given in saline to mice with ongoing clinical EAE suppresses subsequent relapses. However, aggregation of both chimeras allows crosslinking of Fcgamma receptors (FcgammaRs) and induction of IL-10 production by APCs but does not promote the up-regulation of costimulatory molecules. Consequently, IL-10 displays bystander suppression and synergizes with presentation without costimulation to drive effective modulation of EAE. As Ig-PLP1 is more potent than Ig-PLP-LR in the down-regulation of T cells, we conclude that peptide affinity plays a critical role in this multi-modal approach of T cell modulation.
Animals↗
Coupling of peripheral tolerance to endogenous interleukin 10 promotes effective modulation of myelin-activated T cells and ameliorates experimental allergic encephalomyelitis.
Several immune-based approaches are being considered for modulation of inflammatory T cells and amelioration of autoimmune diseases. The most recent strategies include simulation of peripheral self-tolerance by injection of adjuvant free antigen, local delivery of cytokines by genetically altered T cells, and interference with the function of costimulatory molecules. Although promising results have been obtained from these studies that define mechanisms of T cell modulation, efficacy, practicality, and toxicity, concerns remain unsolved, thereby justifying further investigations to define alternatives for effective downregulation of aggressive T cells. In prior studies, we demonstrated that an immunoglobulin (Ig) chimera carrying the encephalitogenic proteolipid protein (PLP)1 peptide corresponding to amino acid sequence 139-151 of PLP, Ig-PLP1, is presented to T cells approximately 100-fold better than free PLP1. Here, we demonstrate that aggregation endows Ig-PLP1 with an additional feature, namely, induction of interleukin (IL)-10 production by macrophages and dendritic cells, both of which are antigen-presenting cells (APCs). These functions synergize in vivo and drive effective modulation of autoimmunity. Indeed, it is shown that animals with ongoing active experimental allergic encephalomyelitis dramatically reduce the severity of their paralysis when treated with adjuvant free aggregated Ig-PLP1. Moreover, IL-10 displays bystander antagonism on unrelated autoreactive T cells, allowing for reversal of disease involving multiple epitopes. Therefore, aggregated Ig-PLP1 likely brings together a peripheral T cell tolerance mechanism emanating from peptide presentation by APCs expressing suboptimal costimulatory molecules and IL-10 bystander suppression to drive a dual-modal T cell modulation system effective for reversal of autoimmunity involving several epitopes and diverse T cell specificities.
Animals↗
High frequency of autoreactive myelin proteolipid protein-specific T cells in the periphery of naive mice: mechanisms of selection of the self-reactive repertoire.
The autoreactive T cells that escape central tolerance and form the peripheral self-reactive repertoire determine both susceptibility to autoimmune disease and the epitope dominance of a specific autoantigen. SJL (H-2(s)) mice are highly susceptible to the induction of experimental autoimmune encephalomyelitis (EAE) with myelin proteolipid protein (PLP). The two major encephalitogenic epitopes of PLP (PLP 139-151 and PLP 178-191) bind to IA(s) with similar affinity; however, the immune response to the PLP 139-151 epitope is always dominant. The immunodominance of the PLP 139-151 epitope in SJL mice appears to be due to the presence of expanded numbers of T cells (frequency of 1/20,000 CD4(+) cells) reactive to PLP 139-151 in the peripheral repertoire of naive mice. Neither the PLP autoantigen nor infectious environmental agents appear to be responsible for this expanded repertoire, as endogenous PLP 139-151 reactivity is found in both PLP-deficient and germ-free mice. The high frequency of PLP 139-151-reactive T cells in SJL mice is partly due to lack of thymic deletion to PLP 139-151, as the DM20 isoform of PLP (which lacks residues 116-150) is more abundantly expressed in the thymus than full-length PLP. Reexpression of PLP 139-151 in the embryonic thymus results in a significant reduction of PLP 139-151-reactive precursors in naive mice. Thus, escape from central tolerance, combined with peripheral expansion by cross-reactive antigen(s), appears to be responsible for the high frequency of PLP 139-151-reactive T cells.
Animals↗
Differential control of neonatal tolerance by antigen dose versus extended exposure and adjuvant.
Ig-PLP1, an immunoglobulin (Ig) chimera carrying the encephalitogenic proteolipid protein (PLP) sequence 139-151 (PLP1), induces neonatal tolerance in mice and confers resistance to experimental allergic encephalomyelitis (EAE) without the need for incomplete Freund's adjuvant (IFA). The mechanism underlying such tolerance involves organ-specific T cell regulation characterized by lymph node deviation and an unusual IFNgamma-dependent splenic anergy. This form of T cell modulation may prove useful for prevention of autoimmunity. However, since the neonatal period is susceptible to regulation, further investigations are necessary to define parameters required to establish regimens suitable for optimal protection against disease. Therefore, studies were carried out to investigate the effect that IFA, the dose of Ig-PLP1, and the number of Ig-PLP1 injections might have on Ig-PLP1-mediated neonatal tolerance and protection against disease. Herein it is reported that as little as 1 microg of Ig-PLP1 supported IFNgamma-dependent splenic anergy but lymph node deviation and protection against disease strengthened as the dose of tolerogen increased. However, when a two-injection regimen was applied, resistance to disease was observed but the mechanism manifested proliferative and cytokine unresponsiveness in both lymphoid organs. Furthermore, the use of IFA along with Ig-PLP1 yielded a suppressive mechanism similar to that of the two-injection regimen. Therefore, the dose of Ig-PLP1 displays a quantitative influence, while the number of injections of Ig-PLP1 and the presence of IFA rather drive qualitative influences on such tolerance.
Adjuvants, Immunologic↗
Neonatal tolerant immunity for vaccination against autoimmunity.
Autoimmunity arises when the immune system no longer tolerates self and precipitates lymphocyte reactivity against our own antigens. Although the developing T cell repertoire is constantly purging, self-recognition events do exist when such tight control is evaded and autoreactive lymphocytes escape the thymus (the sites of T cell development) and migrate to the periphery. Upon activation these autoreactive cells may exert aggressive behavior toward one's own tissues and organs leading to autoimmune disease. Multiple sclerosis, Rheumatoid arthritis, and type I diabetes are autoimmune diseases mediated by autoreactive T cells. A logical approach to prevent such autoimmunity would be to reprogram those lymphocytes to tolerate the self antigen. Injection of antigen at the neonatal stage promotes a state of tolerance such that successive encounter with antigen does not precipitate aggressive reactions. The mechanism underlying neonatal tolerance involves priming of T cells whose effector functions do not cause inflammatory reactions upon recognition of antigen but rather induce protective immunity. This form of tolerant immunity provides an attractive strategy for vaccination against autoimmunity. Herein, it is shown that neonatal exposure to a self-peptide-immunoglobulin chimera drives a tolerant immunity toward the self-peptide and protects against the autoimmune disease, experimental allergic encephalomyelitis.
Animals↗
Differential presentation of an altered peptide within fetal central and peripheral organs supports an avidity model for thymic T cell development and implies a peripheral readjustment for activation.
Altered self peptides may drive T cell development by providing avidity of interactions low enough to potentiate positive selection but not powerful enough to trigger programmed cell death. Since the peptide repertoire in both central and peripheral organs is nearly the same, interactions of these peptides with T cells in the thymus would have to be different from those taking place in the periphery; otherwise, T cell development and maturation would result in either autoimmunity or T cell deficiency. Herein, a self and an altered self peptide were delivered to fetuses, and their presentation as well as the consequence of such presentation on T cell development were assessed. The results indicate that the self peptide was presented in both central and peripheral fetal organs and that such presentation abolished T cell responses to both peptides during adult life. However, the altered peptide, although presented in vivo as well as in vitro by splenic cells, was unable to stimulate a specific T cell clone when the presenting cells were of thymic origin and allowed offspring to be responsive to both peptides. These findings indicate that central and peripheral organs accommodate selection and peripheral survival of T cells by promoting differential altered peptide presentation.
Animals↗
Neonatal exposure to a self-peptide-immunoglobulin chimera circumvents the use of adjuvant and confers resistance to autoimmune disease by a novel mechanism involving interleukin 4 lymph node deviation and interferon gamma-mediated splenic anergy.
Induction of neonatal T cell tolerance to soluble antigens requires the use of incomplete Freund's adjuvant (IFA). The side effects that could be associated with IFA and the ill-defined mechanism underlying neonatal tolerance are setbacks for this otherwise attractive strategy for prevention of T cell-mediated autoimmune diseases. Presumably, IFA contributes a slow antigen release and induction of cytokines influential in T cell differentiation. Immunoglobulins (Igs) have long half-lives and could induce cytokine secretion by binding to Fc receptors on target cells. Our hypothesis was that peptide delivery by Igs may circumvent the use of IFA and induce neonatal tolerance that could confer resistance to autoimmunity. To address this issue we used the proteolipid protein (PLP) sequence 139-151 (hereafter referred to as PLP1), which is encephalitogenic and induces experimental autoimmune encephalomyelitis (EAE) in SJL/J mice. PLP1 was expressed on an Ig, and the resulting Ig-PLP1 chimera when injected in saline into newborn mice confers resistance to EAE induction later in life. Mice injected with Ig-PLP1 at birth and challenged as adults with PLP1 developed T cell proliferation in the lymph node but not in the spleen, whereas control mice injected with Ig-W, the parental Ig not including PLP1, developed T cell responses in both lymphoid organs. The lymph node T cells from Ig-PLP1 recipient mice were deviated and produced interleukin (IL)-4 instead of IL-2, whereas the spleen cells, although nonproliferative, produced IL-2 but not interferon (IFN)-gamma. Exogenous IFN-gamma, as well as IL-12, restored splenic proliferation in an antigen specific manner. IL-12-rescued T cells continued to secrete IL-2 and regained the ability to produce IFN-gamma. In vivo, administration of anti-IL-4 antibody or IL-12 restored disease severity. Therefore, adjuvant-free induced neonatal tolerance prevents autoimmunity by an organ-specific regulation of T cells that involves both immune deviation and a new form of cytokine- dependent T cell anergy.
Adjuvants, Immunologic↗
TCR agonist and antagonist exert in vivo cross-regulation when presented on Igs.
Ig-PLP1 and Ig-PLP-LR are chimeric Igs expressing proteolipid protein (PLP)-derived T cell agonist (PLP1) and antagonist (PLP-LR) peptides, respectively. Both chimeras, like free PLP1 and PLP-LR peptides, induce in vivo-specific T cell responses. However, the responses induced by Ig-PLP1 and Ig-PLP-LR were cross-reactive with both PLP1 and PLP-LR peptides, while those induced by free peptides were not. Surprisingly, despite the cross-reactivity of the responses, when Ig-PLP1 and Ig-PLP-LR were administered together into mice, a dose-dependent down-regulation of both T cell responses and a reduction of IL-2 production to background levels was observed. In contrast, when T cells induced by either Ig chimera were stimulated in vitro with mixtures of free PLP1 and PLP-LR peptides, there was no down-regulation of proliferation or decrease in IL-2 production. These data indicate that Ig-PLP1 and Ig-PLP-LR exert adverse reactions on one another at the level of naive T cells, resulting in an opposite antagonism. However, naive T cells experiencing either chimera develop into cross-reactive cells, acquire resistance to TCR triggering by closely related but different peptides, and support responsiveness.
Animals↗
Presentation of a T cell receptor antagonist peptide by immunoglobulins ablates activation of T cells by a synthetic peptide or proteins requiring endocytic processing.
T cell receptor (TCR) antagonism is being considered for inactivation of aggressive T cells and reversal of T cell-mediated autoimmune diseases. TCR antagonist peptides silence aggressive T cells and reverse experimental allergic encephalomyelitis induced with free peptides. However, it is not clear whether free antagonist peptides could reverse natural disease where the antigen is presumably available for endocytic processing and peptides gain access to newly synthesized class II MHC molecules. Using an efficient endocytic presentation system, we demonstrate that a proteolipid protein (PLP) TCR antagonist peptide (PLP-LR) presented on an Ig molecule (Ig-PLP-LR) abrogates the activation of T cells stimulated with free encephalitogenic PLP peptide (PLP1), native PLP, or an Ig containing PLP1 peptide (Ig-PLP1). Free PLP-LR abolishes T cell activation when the stimulator is free PLP1 peptide, but has no measurable effect when the stimulator is the native PLP or Ig-PLP1. In vivo, Ig-PLP1 induces a T cell response to PLP1 peptide. However, when coadministered with Ig-PLP-LR, the response to PLP1 peptide is markedly reduced whereas the response to PLP-LR is normal. Free PLP-LR coadministered with Ig-PLP1 has no effect on the T cell response to PLP1. These findings indicate that endocytic presentation of an antagonist peptide by Ig outcompete both external and endocytic agonist peptides whereas free antagonist hinders external but not endocytic agonist peptide. Direct contact with antagonist ligand and/or trans-regulation by PLP-LR-specific T cells may be the operative mechanism for Ig-PLP-LR-mediated downregulation of PLP1-specific T cells in vivo. Efficient endocytic presentation of antagonist peptides, which is the fundamental event for either mechanism, may be critical for reversal of spontaneous T cell-mediated autoimmune diseases where incessant endocytic antigen processing could be responsible for T cell aggressivity.
Animals↗
Engineering of doubly antigenized immunoglobulins expressing T and B viral epitopes.
BACKGROUND: Concomitant with the advent of molecular biology techniques and the ability of immunoglobulins (Ig) to recognize proteins, carbohydrates, lipopeptides and nucleic acids, vaccinologists have taken advantage to develop a variety of prophylactic and therapeutic vaccine prototypes. Presentation of epitopes to the immune system by Ig molecules as a carrier platform offers several advantages: (i) long exposure of the antigen to antigen processing cells (APCs) by virtue of their long half life, (ii) lack of the immune response to self Ig, focusing the immune response to protective epitopes rather than irrelevant epitopes, (iii) it takes advantage of the properties of Fc fragment of various isotypes like crossing the placenta (IgG) or homing in epithelia (IgA), and (iv) targeting various antigens by virtue of their binding specificity. OBJECTIVES: This study was aimed to genetically and enzymatically engineer immunoglobulins (Igs) able to express and to deliver concomitantly immunodominant T and B viral epitopes. STUDY DESIGN: Using a genetic engineering approach we replaced the complementary determining region 3 (CDR3) and complementary determining region 2 (CDR2) of an anti-arsonate 91A3 mAb with the immunodominant HA110-120 T cell epitope and HA150-159 B cell epitope of hemagglutinin (HA) of influenza A/PR8 virus, respectively. The second doubly antigenized Ig (Ig-HA-Gal-B) was constructed on an Ig in which CDR3 was replaced with HA110-120 T cell epitope while the HA150-159 B cell epitope was enzymatically assembled through an imidic bond on the galactose (Gal) residues of the carbohydrate moiety. RESULTS AND CONCLUSIONS: Both genetically and genetically/enzymatically doubly antigenized Ig constructs (dAIg) were properly folded and they were able to activate peptide-specific T cells and to elicit anti-viral antibody response in mice. This demonstrates that the CDR loops as well as carbohydrate moieties of immunoglobulins represent permissive sites for grafting foreign epitopes without altering the structural integrity of immunoglobulins and the immunogenicity of the viral peptides.
Animals↗
Purification of antigenized immunoglobulins derivatized with monomethoxypolyethylene glycol.
Genetically engineered immunoglobulins (Igs) carrying viral B or T cell peptides in the CDR3 loop, function as efficient delivery system of the defined viral epitopes. Two of these antigenized Igs (AIgs) were derivatized with 2-O-monomethoxypolyethylene glycol-4,6-dichloro-s-triazine (mPEG). Herein, we describe a two-step strategy to purify mPEG-derivatized AIgs (AIgs-mPEG). Unreacted mPEG polymers were removed by size-exclusion chromatography using ammonium hydrogencarbonate as a buffer system. Mildly PEGylated AIgs were isolated from free and highly derivatized AIgs by anion-exchange chromatography. Electrophoretic analysis indicated that the AIgs-mPEG preparation contained less than 4 x 10(-4) M unreacted mPEG. This strategy may be applied to other mPEG-derivatized monoclonal antibodies.
Animals↗
Derivatization with monomethoxypolyethylene glycol of Igs expressing viral epitopes obviates adjuvant requirements.
Ig molecules expressing within the CDR3 loop viral B or T cell epitopes were derivatized with mPEG 5,000. Pegylated Ig were used to investigate the in vitro and in vivo effect of pegylation on the immunogenicity of viral epitopes expressed in chimeric Ig. Two chimeras were used in this study: Ig-HA carrying a CD4 epitope corresponding to amino acid residues 110-120 of the hemagglutinin (HA) of PR8 influenza A virus and Ig-V3C, a murine-human chimera carrying a consensus B cell epitope from the V3 loop of HIV-1 gp120 protein. Pegylated Ig-HA (Ig-HA-mPEG) with 6 to 8% substituted lysine residues showed in vivo resistance to enzymatic degradation and persisted significantly in blood circulation and lymphoid organs. Moreover, Ig-HA-mPEG was able to activate in vitro HA110-120-specific hybridoma T cells and to prime T cell proliferative response in vivo without requirement for adjuvant. Also, mildly pegylated Ig-V3C (Ig-V3C-mPEG) administered into BALB/c mice in the absence of adjuvant induced specific Ab response to V3C peptide with insignificant response to xenogeneic human Ig determinants.
Adjuvants, Immunologic↗
Induction of antibodies to the human immunodeficiency virus type 1 by immunization of baboons with immunoglobulin molecules carrying the principal neutralizing determinant of the envelope protein.
The hypervariable region 3 (V3) within the disulfide-bridged loop of the envelope protein of the human immunodeficiency virus type 1 (HIV-1) contains an amino acid sequence that was defined as a principal neutralizing determinant (PND). A 19-amino acid residue consensus sequence (designated V3C) predicted from the PND sequences of 245 isolates as well as a sequence from the PND of the WMJ2 HIV-1 isolate (designated V3M) were expressed on the variable region of murine-human immunoglobulin (Ig) chimeras that were designated Ig-V3C and Ig-V3M, respectively. The HIV-1 sequences on the Ig chimeras preserved their antigenicity and interacted with antibodies specific for peptides encompassing the V3C and V3M sequences. In baboons, Ig-V3C and Ig-V3M induced antibodies that bound V3C and V3M peptides as well as the glycoprotein gp120 envelope protein of HIV-1 MN isolate. In addition, the baboons' antisera were able to prevent infection of CD4 SupT1 susceptible T cells by HIV-1 MN. Finally, Ig-V3M chimeras were able to stimulate in vitro production of antibodies specific for the HIV-1 envelope-derived peptides by lymphocytes from HIV-1-infected human subjects.
AIDS Vaccines↗