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Invariant Chain (invariant + chain)
Selected AbstractsTherapeutic human papillomavirus DNA vaccination strategies to control cervical cancerEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2007T.-C. Wu Abstract A persistent human papillomavirus (HPV) infection is considered causal and necessary for the continued growth of cervical cancer. Thus, vaccination against HPV represents a plausible approach to prevent and treat cervical cancer. A report in the current issue of the European Journal of Immunology describes a therapeutic HPV DNA vaccination strategy using the HPV-16 E7 antigen fused to the invariant chain to enhance the E7-specific CD8+ and CD4+ T cell immune responses, resulting in a potent anti-tumor effect against E7-expressing tumors. Continued exploration of HPV therapeutic DNA vaccines may lead to eventual clinical application. See accompanying article http://dx.doi.org/10.1002/eji.200636233 [source] DNA vaccine encoding endosome-targeted human papillomavirus type,16 E7,protein generates CD4+ T cell-dependent protectionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2007Jean-Marc Brulet Abstract Human papillomavirus type,16 is commonly implicated in cervical cancers. The viral genome encodes potential targets like the oncoprotein,E7, expressed in transformed cells but thought to represent a poorly immunogenic antigen. We describe in this work a DNA-based vaccination protocol aimed at inducing an efficient anti-E7 immune response in vivo. Plasmids allowing the expression of the E7,protein in distinct cellular compartments were generated and assayed in an in vivo model of tumor growth. Our data demonstrate that mice vaccinated with a plasmid encoding for an E7,protein fused to a domain of the MHC class,II-associated invariant chain (IiE7) were protected against tumor challenge. Mice immunized against an ubiquitinated form of E7 (Ub(Ala)E7) failed to control tumor growth. Protection induced by IiE7 was correlated with the development of CD8+ CTL and required the presence of CD4+ cells. In vitro studies confirmed that the IiE7 fusion protein was expressed at high levels in the endosomal compartment of transfected cells, while the natural and the ubiquitin-modified form of E7 were mainly nuclear. The present study suggests that an efficient anti-tumor response can be induced in vivo by DNA constructs encoding for E7,protein forms localizing at the endosomal compartment. See accompanying commentary: http://dx.doi.org/10.1002/eji.200636233 [source] The cytoplasmic tail of invariant chain modulates antigen processing and presentationEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2003Abstract The MHC class II-associated invariant chain (Ii) has several important functions in antigen presentation. In this study, we have examined the effect of Iip33 expression on endocytic transport and antigen presentation. We find that degradation of both endocytosed antigen and Ii itself is delayed in cells expressing high levels of Ii, whereas a mutant Ii with an altered charge distributionin the cytoplasmic tail was unable to exert this effect. Furthermore, the Ii mutant did not enhance the presentation of an Ii-dependent MHC class II-restricted epitope to the same extent as the wild type. In a parallel study, we investigated the effect of charge in the cytoplasmic tail of Ii. We find that due to exposed negative charges, it promotes endosome fusion events, and we suggest thatthis causes endosomal retention (Nordeng et al., Mol. Biol. Cell 2002). Together, the data reveal an additional property of the Iip33 cytoplasmic tail that contributes to the modulation of antigen processing and presentation. [source] Targeting the MHC class II pathway of antigen presentation enhances immunogenicity and safety of allergen immunotherapyALLERGY, Issue 1 2009J. M. Martínez-Gómez Background:, Current s.c. allergen-specific immunotherapy (SIT) leads to amelioration of IgE-mediated allergy, but it requires numerous allergen injections over several years and is frequently associated with severe side-effects. The aim of this study was to test whether modified recombinant allergens can improve therapeutic efficacy in SIT while reducing allergic side-effects. Methods:, The major cat allergen Fel d 1 was fused to a TAT-derived protein translocation domain and to a truncated invariant chain for targeting the MHC class II pathway (MAT-Fel d 1). The immunogenicity was evaluated in mice, while potential safety issues were assessed by cellular antigen stimulation test (CAST) using basophils from cat-dander-allergic patients. Results:, MAT-Fel d 1 enhanced induction of Fel d 1-specific IgG2a antibody responses as well as the secretion of IFN-, and IL-2 from T cells. Subcutaneous allergen-specific immunotherapy of mice using the modified Fel d 1 provided stronger protection against anaphylaxis than SIT with unmodified Fel d 1, and MAT-Fel d 1 caused less degranulation of human basophils than native Fel d 1. Conclusion:, MAT-Fel d 1 allergen enhanced protective antibody and Th1 responses in mice, while reducing human basophil degranulation. Immunotherapy using MAT-Fel d 1 allergen therefore has the potential to enhance SIT efficacy and safety, thus, shortening SIT. This should increase patient compliance and lower treatment costs. [source] Diversification in MHC class II invariant chain-like proteins among fishesJOURNAL OF APPLIED ICHTHYOLOGY, Issue 4 2004M. Sakai Summary The major histocompatibility complex (MHC) class II invariant chains are important for an efficient and complete presentation of antigens by MHC class II molecules. Invariant chain-like proteins (Iclp) 1 and 2 were identified by expressed sequence tag analysis from cDNA library of common carp head kidney (HK) stimulated with concanavalin A and lipopolysaccharide. The sequences were 1043 and 1016 bp in length encoding 234 and 198 amino acid proteins, respectively. Based on their predicted structure, the genes harboured transmembrane domain (TMD) and Tg (thyroglobulin) type 1 domains. Expression analysis revealed that both genes were expressed in normal tissues of HK, intestine, brain and gill. By database search, similar homologues were found in Atlantic salmon, fugu and catfish. Phylogenetic and alignment analysis indicate diversity among fish Iclps. [source] | ||||||||||