Recombinant Newcastle disease virus vaccine vector (rNDV) on its own induces IFN-alpha and IFN-beta production and DC maturation. Immunization with rNDV encoding anti-DEC205 and HIV-1 gag antigen enhanced CD8+ gag specific T-cell responses and increased the number of CD4+ and CD8+ T cells in the spleen compared to rNDV encoding gag antigen alone [185]. Furthermore, mice were protected against challenge
Inhibitors,research,lifescience,medical of recombinant vaccinia virus expressing HIV gag protein [185]. Conjugation of anti-NLDC-145 monoclonal antibody (monoclonal antibody against murine DEC205) to a model antigen stimulated both antibody and T-cell responses in animal models [186]. Conversely, using a self antigen, proteolipid protein (PLP139-151) conjugated to anti-DEC205 monoclonal antibody tolerized T cells in vivo and reduced the secretion of IL-17 by CD4+ T cells and in vitro CD4+Vbeta6+ T-cell receptor T cells specific for PLP139-151
became anergic [187]. Hence, targeting self-antigens to DEC-205 induces tolerance. It is clear that, targeting DCs using DEC-205 directed antibody-antigen Inhibitors,research,lifescience,medical conjugates represents a novel method of inducing tolerance to self-antigens and antitumor immunity in vivo. 4. Scavenger Receptor The scavenger receptors (SRs) are a group of receptors that recognize modified low density lipoprotein (LDL) by oxidation (oxLDL) or acetylation Inhibitors,research,lifescience,medical (acLDL) (Figure 1). Scavenger receptor Inhibitors,research,lifescience,medical was given its name based on its “scavenging” function. SR is primarily present on macrophages internalize endotoxins, oxLDL, and other negatively charged proteins. SR, are grouped into classes A, B, and C according to their
structural features. (i) Scavenger receptor class A (SR-A1, SR-A2) is mainly expressed on macrophages as a trimer and has 6 domains (cytosol, transmembrane, spacer, alpha-helical coiled-coil, collagen-like, and cystein-rich domains) (Table 2). Members include SCARA1 (MSR1), SCARA2 (MARCO), SCARA3, Inhibitors,research,lifescience,medical SCARA4 (COLEC12), and SCARA5. (ii) Class B (SR-B1) has 2 transmembrane regions and are identified as as ocLDL receptors. Members include SCARB1, SCARB2, and SCARB3 (CD36). (iii) Class C has a transmembrane region in which the N-terminus is located extracellularly. There are other receptors that have been reported to bind to oxLDL which include CD68 and its murine homolog macrosialin, mucins, and LOX-1. Despite the scavenging functions of SR, SRs have been shown to endocytoze antigens and present antigens to MHC class only I and II and stimulate effective CD4+ and CD8+ T-cell responses. Using 200nm particles coated with oligonucleotide polyguanylic acid (SR-targeting agent) showed specific binding to SR, and particles were Microbiology inhibitor localized in intracellular vesicles and processing via the endocytotic pathway [188]. An early example demonstrating immune responses generation was with maleylated OVA which bound to SR, enhancing its presentation and stimulation of CTLs by macrophages and B cells [189].