![]() Downstream of the V, D, and J genes are constant (C) region exons, which encode the C-terminus of all TCRs and couples the TCR to the Cluster of differentiation 3 (CD3) protein complex to mediate signal transduction into the T cell. Recombination of V, D, and J segments leads to a gene fragment that encodes the V-region domain, which becomes the N-terminus of the TCR protein and determines its antigen specificity. Instead, the TCR loci encode families of variable (V), diversity (D), and joining (J) segments, which undergo rearrangement early during T cell development. The germline configuration of TCR genes is not functional. TCR repertoire diversity arises through genetic mechanisms that minimize the number of genetic elements encoded by the genome while maximizing the potential breadth of expressed TCRs. The tremendous capacity of T cells to recognize diverse antigens has a genetic basis that is inherent in the genomic organization of the T cell receptor (TCR) loci. Thus, the cynomolgus macaque is providing insights into human disease not possible with other small animal models. tuberculosis-infected cynomolgus macaques recapitulates the spectrum of human TB pathology. ![]() tuberculosis, nearly half of infected cynomolgus macaques develop a form of disease that resembles latent TB in people. However, Flynn’s group finds that following challenge with low dose M. Most NHP species, including rhesus macaques, whether in captivity or in the wild, rapidly succumb to Mycobacterium tuberculosis infection. Importantly, they are increasingly used for infectious disease research, including as a model for human HIV and SARS-CoV2 infection. Cynomolgus macaques have been increasingly used for biomedical research, especially in the fields of neurology, cardiology, and for drug development. Consequently, the rhesus macaque’s TCR locus was among the first NHP TCR locus to be characterized. For HIV research, the field largely turned to nonhuman primates (NHP) as a better alternative because they could be infected with a highly related virus, Simian Immunodeficiency Virus (SIV). Mice are naturally resistant to both infections. Two important examples are acquired immunodeficiency syndrome (AIDS), which is caused by the Human Immunodeficiency Virus-1 (HIV-1), and COVID-19, which is caused by the SARS-CoV2 coronavirus. This has been repeatedly emphasized for cancer and is also true for many infectious diseases. However, it is not surprising that many human diseases are inadequately modelled in mice. As part of this effort, the murine TCR repertoire have been extensively characterized and its knowledge is being used to develop new approaches to facilitate antigen discovery and novel treatments for human disease. The mouse has been incredibly useful in elucidating the major concepts of immunology, including defining the genetic and molecular basis of immunoglobulin and TCR formation and diversity. The Creative Commons Public Domain Dedication waiver ( ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.Įxperimental animal models are an essential tool in our pursuit of understanding human physiology. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |