China
Africa
Explore chapters and articles related to this topic
Clinical Applications of Gene Therapy for Immuno-Deficiencies
Published in Yashwant Pathak, Gene Delivery, 2022
Khushboo Faldu, Sakshi Gurbani, Jigna Shah
RAG1 gene defects impair the functioning of T-cells due to variable (V), diversity (D), and joining (J) genes-VDJ recombination faults and, consequently, lead to the development of abnormal T-cell receptor (TCR) and Ig receptor reorganization. Additionally, these patients are predisposed to develop malignancies [43]. Treatment with alloHSCT is challenging, as patients suffering from Artemis SCID bear a mutation that confers on them sensitivity to radiotherapy or alkylating chemotherapy, which is utilized in preconditioning to achieve optimal immune reconstitution [44]. SIN-LV vector carries Artemis cDNA and endogenous promoter. It potentially restores B and T-cells after transducing the CD34+ cells of Artemis SCID patients, and corrects radiosensitivity in patients’ fibroblasts [44, 45].
Phylogeny of the mucosal immune system
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Robert D. Miller, Irene Salinas
In birds, B cells that have undergone V(D)J recombination in the bone marrow must migrate to the bursa to complete their development. In the bursa of Fabricius, avian B cells complete their development by introducing mutations into their recombined V genes using AID-mediated gene conversion. This is an essential step because of the lack of repertoire diversity generated by V(D)J recombination alone. The chicken IgH locus contains only a single functional V gene and a large array of nonfunctional V pseudogenes. Although the pseudogenes cannot be recombined and expressed, they can be used as a source of donor sequences for gene conversion (Figure 2.4).
Dopamine in the Immune and Hematopoietic Systems
Published in Nira Ben-Jonathan, Dopamine, 2020
B lymphocytes also develop from hematopoietic progenitors in the bone marrow, where they undergo the initial process of differentiation and selection [6]. They are distinguished from T cells and NK cells by the expression of the B cell receptor (BCR) on their plasma membrane. Development of B cells occurs in several stages, marked by various patterns of gene expression, and an arrangement of the immunoglobulin H chain and L chain gene loci. They also undergo the V(D)J recombination of their immunoglobulins. To complete their development, immature B cells migrate from the bone marrow to the spleen. Once fully differentiated, B cells can secrete antibodies and comprise the humoral component of the adaptive immunity. In addition, B cells present antigen and secrete cytokines. The BCR enables each B cell clone to bind a specific antigen and initiate an antibody response. Activation of B cells occurs via antigen recognition by BCRs and requires a secondary activation signal provided either by T helper cells or by the antigen itself.
Electrostatic Complementarity of T-Cell Receptor-Alpha CDR3 Domains and Mutant Amino Acids Is Associated with Better Survival Rates for Sarcomas
Published in Pediatric Hematology and Oncology, 2021
Michelle Yeagley, Boris I. Chobrutskiy, Etienne C. Gozlan, Nikhila Medikonda, Dhruv N. Patel, Shayan Falasiri, Blake M. Callahan, Taha Huda, George Blanck
Two hundred sixty-two whole exome sequence (WXS) files for TCGA-SARC case IDs representing 261 soft tissue sarcoma (STS) patients were recovered from the genomic data commons (GDC) (https://portal.gdc.cancer.gov/repository) per National Center for Biotechnology Information’s Database of Genotypes and Phenotypes (dbGaP) approved project number 6300. (In one case, there was both a metastatic and primary tumor sample represented by a WXS files, respectively. In all other cases, only a primary tumor sample was used to prepare the WXS files.) Immune receptor V(D)J recombination reads were recovered using previously published and extensively benchmarked processes,19 with read validations based on known V and J sequences obtained from The International Immunogenetics Information System (http://www.imgt.org/). The CDR3 domains of the V(D)J recombination reads were then identified and translated. Both processes were performed using a previously described algorithm,17 and the original script is at github.com (https://github.com/bchobrut-USF/lgg_idh1). The net charge per residue (NCPR) was calculated for each CDR3 using the localCIDER python package (http://pappulab.github.io/localCIDER/).
A public-private partnership for the express development of antiviral leads: a perspective view
Published in Expert Opinion on Drug Discovery, 2021
The prediction of ligand-protein affinity is expected to be performed by a self-programming artificial-intelligence processor, which operates on a long list of potential features and mathematical forms (‘kernels’) for the characterization of the promising signatures [56]. This diversity mimics the bionic principles of optimization, existing in the evolution of antibody affinity in response to the infective agent termed V(D)J recombination [57]. In the V(D)J recombination process, the germline population of B and T cells ‘fit’ the antigens to the practically infinite plurality of recombination variants, choosing the optimal (affinity complex forming) variant for the clonal amplification. In the algorithmic solution mimicking this natural principle, the optimization of affinity prediction is achieved by testing a plurality of classification feature sets and mathematical forms in a self-programming mode [58]. Many approaches can be borrowed from the experience with the AI-driven self-driving cars, where the classifiers differentiate between the safe and unsafe situations based on the progressive self-learning capability [59].
Approaches to patients with variants in RAG genes: from diagnosis to timely treatment
Published in Expert Review of Clinical Immunology, 2019
Adeeb A. Bulkhi, Joseph F. Dasso, Catharina Schuetz, Jolan E. Walter
Genetic testing is the first affirmative step for RAG deficiencies. However, a cautious approach needs to be practiced when interpreting genetic results. It is known that RAG genes are highly polymorphic and, many times, VUS are being identified. Therefore, it is recommended that the novel mutant RAG gene is functionally tested for relative recombinase activity. In vitro assays are available in single allele and bi-cistronic systems (for compound heterozygous mutations) on a research basis. In vivo assessment of RAG function can be drawn from T and B cell receptor (TCR and BCR) repertoire studies. Some of these studies are extensive and can be accomplished on the grounds of research collaboration with laboratories that focus on V(D)J recombination. However, recently simplified tools are emerging that may be used for in vivo validation of novel hypomorphic RAG variants. These may include flow cytometry or PCR-based detection of certain TCR-Vα segments in immune cells. Curiously, antibodies targeting cytokines (IFN-α, IFN-⍵, and IL-12) have been detected in a high fraction of the patients and may be used as possible biomarkers.