The use of molecular genetics over the past few decades has helped us elucidate the mechanisms of action of the immune system in a variety of diseases, including cancer. MHC class I and class II complexes determine the specificity and affinity of peptide binding and T cell recognition due to their high degree of polymorphism. To restore the polymorphism of human MHC at the lowest possible cost, Creative Biolabs has established a humanized class I and class II molecular transgenic mouse model, to help our clients solve various problems in the development of drugs, including the evaluation of tumor antigen-binding ability.
HLA Transgenic Mice as Humanized Mouse Models for Drug Development
HLA molecules play a key role in thymic T cell bank selection and peripheral antigen presentation. Analysis of T cell responses in humans involves the use of T cell lines or clones of naturally elicited individuals in vitro. At present, scientists have determined the MHC restriction, the location of mouse epitope recognition and T cell function through in vivo studies. Various animal models represented by transgenic mice have made great contributions to our study of the immune system. However, in the field of cancer immunotherapy, the process of antigen recognition by immune cells is complicated. Since the mouse MHC gene is different from humans, we need to make a more accurate assessment of the immunogenicity of the target antigen. The production of transgenic mice expressing functional HLA molecules is an important step in establishing a human-like in vivo model to enhance our understanding of the function of human molecules in disease induction and susceptibility.
Fig.1 HLA molecules in transgenic mice lacking endogenous class II molecules can shape the T cell repertoire in the thymus of mice.
MHC I + MHC II Double Transgenic Mice
Many research groups are now developing mouse models that produce human MHC class I and class II. Creative Biolabs' MHC double transgenic mice established by hybridization technology can simultaneously express chimeric MHC class I and II molecules and exclude MHC interference from mice themselves. These mice represent a versatile animal model for studying the immunogenicity of HLA CTL epitopes in the absence of a murine MHC response. The established animal model will also be useful for evaluating and optimizing T cell-based vaccines and for studying differences in antigen processing between mice and humans. In addition, these mice can also study tolerance to specific tumor antigens and how to understand the role of the antigen.
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