Creative BioMart is a well-known expert who is committed to developing a variety of protein therapies to improve the effectiveness and safety of protein therapy, and to allow the production of new types of proteins and effects. With years of experience, we provide customized services for major histocompatibility complex as protein therapeutics to precisely meet customer requirements.

Introduction of Therapeutic Major Histocompatibility Complex

Antigen presentation by major histocompatibility complex (MHC) classⅠ and Ⅱ proteins is critical for acquired immunity. Immunogenic peptide-MHC class Ⅰ(pMHCⅠ) complexes are present on nucleated cells and are recognized by cytotoxic CD⁸⁺ T cells. On the other hand, presentation of pMHCⅡ by antigen presenting cells such as dendritic cells, macrophages or B cells can activate CD⁴⁺ T cells, leading to the coordination and regulation of effector cells. Disorders of the MHC system are associated with many diseases, such as malaria, rheumatoid arthritis, type I diabetes and transplant rejection. Therefore, researchers are working to develop MHC-based immunotherapy and immunodiagnostics with significant results. Such as pMHC tetramer, a multimeric form of peptide-MHC complexes, which enables direct detection and identification of antigen-specific T cells, modulation of T cell responses in vivo to treat graft rejection and autoimmune diseases, and detailed monitoring of cellular immune responses induced by immunotherapy.

Fig 1. Multimers of pMHC molecules are soluble reagents capable of binding cognate T cells. (Gojanovich G S, et al., 2012)

Services

Therapeutic monoclonal antibodies targeting cell surface or secreted antigens are one of the most effective classes of novel immunotherapies. However, most human proteins and established cancer biomarkers are intracellular. MHC class Ⅰ molecules present short peptides derived from endogenous and exogenous proteins to associate with T cell receptors (TCRs) on the surface of T cells. Most pMHC tetramers are difficult to produce recombinantly and are limited by the low affinity of pMHC monomers. As a leading service provider of protein engineering, Creative BioMart has established a powerful MHC-based protein therapeutics platform to design MHC molecules with improved solubility or higher TCR binding affinity. In addition, peptide-binding specificity and promiscuity of MHC alleles were characterized by high-throughput yeast surface display technology.

Studies have shown that pMHC multimers have been used to visualize T cell effector expansion and islet invasion during diabetes development. Our scientists utilize selective amino acid side chain labeling protocols for more complex NMR experiments, methods that rely on CEST or relaxation dispersion combined with protein engineering approaches using different expression systems to design therapeutic MHC molecules. Our success stories include:

1. pMHC multimers: our engineered chimeric human and mouse pMHC tetramers can recognize extremely rare T cells with frequencies less than 10^-5.
2. Single-chain trimers (SCTs): our designed SCTs have been widely used to generate different mouse and human pMHC, which are used to express soluble in bacterial or insect cells. Recombinant proteins, and expression of cell membrane-associated proteins in mammalian cells by transfection or transduction.

Creative BioMart is committed to developing soluble pMHC multimers that specifically bind to selected T cell populations for global pharmaceutical companies, offering promise in the treatment of autoimmune diseases such as type 1 diabetes. We will work with you to develop the most appropriate strategy and provide the most meaningful data for your research for accelerating the research of life sciences. If you are interested in our services, please do not hesitate to contact us for more information.

References

1. Wieczorek M, Abualrous E T, Sticht J, et al.. (2017) Major histocompatibility complex (MHC) class I and MHC class II proteins: conformational plasticity in antigen presentation. Frontiers in immunology. 8: 292.
2. Gojanovich G S, Murray S L, Buntzman A S, et al.. (2012) The use of peptide-major-histocompatibility-complex multimers in type 1 diabetes mellitus. Journal of diabetes science and technology. 6(3): 515-524.

• Engineering of Therapeutic Antibodies
• Engineering of Therapeutic Coagulation Factors
• Engineering of Therapeutic Cytokines and Receptors
• Engineering of Therapeutic Enzyme
• Engineering of Therapeutic Protein Hormones
• Engineering of Therapeutic T Cell Receptors
• Engineering of Therapeutic TCR-Like Antibodies