China
Africa
Explore chapters and articles related to this topic
Host Defense and Parasite Evasion
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2023
Eric S. Loker, Bruce V. Hofkin
Approximately 15 VSG expression sites are found on the subtelomeric portions of particular trypanosome chromosomes. These expression sites have certain features in common. They all contain a promoter site, a region of repetitive DNA called the 70-Base pair repeat, and one functional VSG gene adjacent to the telomere (Figure 4.28). The VSG genes themselves are found in three different locations and the manner in which antigenic switching occurs appears to vary with the location of the VSG genes in question. For those subtelomeric VSG genes located adjacent to promoters, switching is believed to rely on allelic exclusion, the expression of only one of various alternative alleles at a particular time. The expression site that is active at a particular time appears to be located in a particular site within the nucleus, and this site has room for only a single promoter and VSG gene at a time. Subsequently, a nuclear reorganization occurs in which the previously active promoter and adjacent VSG gene are replaced by a new promoter–VSG gene combination. The newly expressed VSG variant protein will now replace the previously expressed protein on the parasite surface. Allelic exclusion as a mechanism to generate antigenic variation appears to occur early in infection of the vertebrate host, before the transition from metacyclic to blood form trypomastigote.
T Cells:Regulation and Cellular Immunity
Published in Constantin A. Bona, Francisco A. Bonilla, Textbook of Immunology, 2019
Constantin A. Bona, Francisco A. Bonilla
In contrast to Ig light chains, the productive rearrangement of one a locus and the expression of an αβ heterodimer does not stop a gene rearrangement, and it is possible to have one cell with two productively rearranged a loci (approximately 25% of a small number of T cells analyzed). In some instances, one a chain is incapable of forming a heterodimer with the expressed β such that only one heterodimer ever appears on the cell surface. In this way there is phenotypic allelic exclusion even if there is not genotypic exclusion. However, T cells expressing two different a chains in complete heterodimeric receptors have been described. The extent to which they contribute to the total T cell population remains to be seen.
Genetics of immunoglobulins: Ontogenic, biological, and clinical implications
Published in Gabriel Virella, Medical Immunology, 2019
One of the most fascinating observations in immunology is that immunoglobulin heavy-chain genes from only one of the two homologous chromosomes 14 (one paternal and one maternal) are expressed in each B lymphocyte. Recombination of VDJC genes described earlier usually takes place on one of the homologues. Only if this rearrangement is unproductive (i.e., it does not result in the secretion of an antibody molecule), does the other homologue undergo rearrangement. Consequently, of the two H chain alleles in a B cell, one is productively rearranged, and the other is either in the germline pattern or is aberrantly rearranged (in other words, excluded). Involvement of the chromosomes is random; in one B cell, the paternal allele may be active, and in another, it may be a maternal allele. (Allelic exclusion is reminiscent of the X-chromosome inactivation in mammals, although it is genetically more complex.)
DNA methylation abnormalities in atherosclerosis
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Samira Tabaei, Seyyedeh Samaneh Tabaee
DNA methylation is one of important epigenetic mechanisms which causes gene suppression [11]. DNA methylation involves in many cellular phenomena such as X-chromosome inactivation, transposable retro element activities, cell differentiation, cell reprogramming, cell death, cell survival, parental gene imprinting, immune system activities and allelic exclusion of immunoglobulin genes [12,13]. DNA methylation abnormalities are linked with different diseases such as cancer, autoimmune diseases and atherosclerosis [14–19]. Investigations on DNA methylation in patients with atherosclerosis documented that there is a unique profile of DNA methylation in this disease, and emphasize on the different pathways and genes which are implicated in the disease [20]. More researches are required to illustrate the DNA methylation signature and the underling mechanism of these modifications in atherosclerosis disease. With clarification and characterization of these abnormalities, we hope that this knowledge may be applied in the diagnosis and treatment of atherosclerosis patients. This review emphasizes on the recent knowledge in DNA methylation abnormalities and their roles in the pathogenesis and progression of atherosclerosis.
10th European immunogenicity platform open symposium on immunogenicity of biopharmaceuticals
Published in mAbs, 2020
S. Tourdot, A. Abdolzade-Bavil, J. Bessa, P. Broët, A. Fogdell-Hahn, M. Giorgi, V. Jawa, K. Kuranda, N. Legrand, S. Pattijn, J. A. Pedras-Vasconcelos, A. Rudy, P. Salmikangas, D. W. Scott, V. Snoeck, N. Smith, S. Spindeldreher, D. Kramer
Dr. Juliana Bessa, from Roche, Switzerland, further discussed protein impurities, including antibody aggregates, and in particular the formation of neo-epitopes as potential risk factors related to the immunogenicity of biologics. The immunogenic properties of soluble antibody aggregates as well as sub-visible particles have been studied in the Roche human IgG1 transgenic (Tg) mouse immunogenicity model. The immunogenicity mouse model consists of a transgenic mouse expressing a mini-repertoire of soluble human IgG1 antibodies. Elimination of membrane Ig-H chain expression was intended to avoid allelic exclusion of endogenous mouse Ig genes. The expressed transgenic repertoire represents the most commonly used antibodies (V genes) in humans and therapeutic antibodies. Immunogenicity of antibody aggregates of different sizes generated under different stress conditions (low pH, process-related and harsh UV-light) was assessed in the current study. Moreover, sub-visible particles of 15 μm size, generated with different oxidizing agents were also tested. Collectively, their findings demonstrated that both soluble aggregates as well as sub-visible particles carrying neo-epitopes derived from extensive covalent modifications in the primary structure of the protein are immunogenic and break immune tolerance in the transgenic mouse model. In contrast, aggregates and/or sub-visible particles of same size but devoid of chemical modifications were not immunogenic in the same model. The role of aggregate size in tolerance breakdown was addressed using IgG1 monomers and preparations carrying increasing amounts of high molecular weight aggregates. As both modified monomers and preparations carrying low contents of large aggregates failed to elicit an immunogenic response, the role of size in tolerance breakdown was also established. The results presented showed that T-cell neo-epitopes are required for immunogenicity of antibody aggregates in a pre-clinical immunogenicity mouse model. As the Ig repertoire covered by the transgenic mice is broad and comprises V families commonly used in therapeutic antibodies, the model can be consistently applied as a pre-clinical tool to assess antibody format- and mechanism-related immunogenicity of therapeutic antibodies across the Roche portfolio.