MHC Class II-associated li Protein Suppression Technology

Creative Biolabs has established an effective vaccine platform based on Ii suppression technology to inhibit the expression of major histocompatibility complex (MHC) class II-associated invariant chain protein (Ii). With our extensive experience and advanced platform, we are therefore confident in offering the best li protein suppression services to our customers around the world to promote the development of vaccine programs.

Ii (Invariant Chain) Protein and Interaction with Class II Molecules

The cell surface form of the invariant chain (li) is called CD74, which is a type II protein consisting of a short cytoplasmic tail, a transmembrane region, and a luminal domain. The luminal domain can be further divided into a proximal membrane disorder region, major MHC II interaction sequence (CLIP) and a C-terminal trimerization domain. The invariant chain has multiple functions but is best characterized as the chaperone polypeptide involved in the formation and transport of major MHC class II (MHCII). Synthesized with MHCII, invariant chain can be viewed as follows, depending primarily on the ability of its CLIP region to occupy the peptide groove of MHCIIs.

  • A GUARDIAN which controls the entry of MHCII groove
  • A SCAFFOLD which helps fold and pair the alpha and beta MHC II chains
  • A LEADER that directs MHCII into the endosomal pathway. It has been determined that these Ii functions are primarily dependent on the ability of their CLIP regions to occupy the peptide groove of MHC II.

Models of the Ii Chain Trimer and the MHC Class II–Ii Chain Complex

Fig.1 Models of the Ii Chain Trimer and the MHC Class II–Ii Chain Complex. (Cresswell P. 1996)

li Suppression Technology for DNA Vaccine

Creative Biolabs has established an effective DNA vaccine platform based on Ii suppression technology to inhibit the expression of major histocompatibility complex (MHC) class II-associated invariant chain protein (Ii), that augments CD4+ T cell activation by endogenously synthesized antigens. The MHCII-associated invariant chain is able to prevent MHC class II molecules from binding to endogenously produced antigenic epitopes. Ii inhibition results in MHCII endogenous antigen presentation by APC without disrupting MHC class I presentation. The core of this platform is to produce an effective vaccine by inhibiting Ii with Ii antisense oligonucleotides, which also effectively inhibits Ii expression in dendritic cells (DC), resulting in the presentation of endogenously expressed ovalbumin (OVA) epitopes to CD4+ T cells and a potent tumor vaccine. The addition of Ii inhibition technology to DNA vaccines significantly improved the efficacy of vaccines with enhanced antigen-specific CD4+ T cell activation. Our platform has significant benefits in terms of treatment or as a preventive vaccination.

Cancer Immunotherapy by Antisense Suppression of Ii Protein

Ii protein suppression, as a promising antisense drug therapy, significantly enhances the immunogenicity of antigenic epitopes presented by tumor cell major histocompatibility complex class II. Our Ii suppression technology platform can create effective tumor cell vaccines by suppressing Ii protein in the presence of MHC class II molecules within MHC-class-II-positive tumor cells. The lack of the Ii protein, which normally blocks the antigen-peptide binding site of MHC II during endoplasmic reticulum synthesis, may increase the range of cancer-associated epitopes presented to CD4+ helper T cells. Effective inhibition of the Ii protein can be achieved with antisense phosphorothioate oligonucleotides, with the advantage that antisense only requires transient efficacy in a small fraction of tumor cells. The resulting systemic anti-tumor immune response eradicates directly treated cells and distant tumor deposits.

Creative Biolabs is a leader in the field of vaccine development and has focused on the cancer vaccines for years. We have experienced experts and advanced platforms that are able to provide excellent services. If you are interested in our services, please contact us for more details.

Reference

  1. Cresswell P. Invariant chain structure and MHC class II function. Cell. 1996, 84(4):505-7.

Our services are for research use only. We do not provide services directly to individuals.

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