Due to the high polymorphism of leukocyte antigens and the immune escape mechanism of tumors, the identification and evaluation of T lymphocyte epitopes are critical for current cancer treatment research. Creative Biolabs evaluates the availability of new Class I and Class II restricted target antigens in different ways. We use in vivo models of transgenic mice to evaluate the immunogenicity of the peptide during treatment to better address complications before or after clinical trials during pre-clinical development.
Screening and Detection of Immunogenic Peptides
Predicting antigenic determinants from tumor antigens by "reverse immunology" represents a potential target in immunotherapy. After the selection of the target antigen and prediction of potential T cell epitopes, the immunogenicity can be synthesized and screened in an in vitro assay or in an in vivo model for natural processing and presentation in the major histocompatibility complex (MHC). This approach has largely replaced the need to produce overlapping peptides for almost the entire target protein; greatly reducing the cost of research and the amount of work required to identify novel T cell epitopes.
Once peptides have been identified using one or more database search methods, they can be synthesized and their ability to bind to appropriate HLA alleles can be further evaluated. Usually, HLA stability test can be used in combination with other tests to evaluate peptide binding. Besides, after each candidate peptide is synthesized, its immunogenicity can be examined by different reverse immunization methods. Synthetic peptides can be used in the in vitro T cell sensitization experiments or in vivo immune transgenic mice.
HLA-A2 Transgenic Mouse Model, HHD II
HHD II mice provide a good animal model for in vivo studies of HLA-A2-restricted cytotoxic T-lymphocyte (CTL) responses. These animals express a single MHC class I molecule a1 and a2 domain consisting of human HLA-A2.1, murine H-2Dba3, transmembrane and cytoplasmic class I heavy chain regions covalently linked to human b2-microglobulin, allowing HLA-A2 restricted antigen presentation. Studies have shown that these animals respond to human p53 peptides by performing HLA-A2 restricted responses to antigenic determinants previously defined in humans, and they are indeed superior to HLA-A transgenic mouse models. HHD II mice have a kill rate of almost 40% compared to traditional HLA-A transgenic mice. This is usually accompanied by strong IFN-γ production.
Creative Biolabs has established an ideal model for the identification of novel immunogenic peptides in HHD II mice, as well as for the preclinical evaluation of vaccine constructs. However, it should be noted that the library of peptides produced by HHD II mice for endogenous processing of some virus-derived proteins is different from humans, and caution is needed when interpreting the data obtained using these mice.
If you have any questions about our MHC I (HLA-A2) transgenic mice, you can contact us by email or send us an inquiry to find a complete solution.
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