Recognition of autoantigens by T cells with self-reactive TCRs can result in tissue-specific damage of systemic autoimmune diseases ( Seiringer et al., 2022). T cells and their receptors are crucial in autoimmunity. Once naïve T cells encounter the peptide-MHC complex (pMHC) presented by an APC, these T cells will start to undergo clonal expansion while retaining the initial TCR sequence ( Huang et al., 2019). The diversity of the αβ TCR from the unique pairing of various gene segments or loci generates on the order of 10 18 or more possible combinations ( Murphy and Weaver, 2022). The rearrangement leads to a vast diversity of TCR repertoires capable of recognizing almost any peptide presented by MHC molecules ( Mitchell and Michels, 2020). This process helps to ensure that only mature T cells respond to foreign antigens exclusively are allowed to survive and develop ( Schatz and Ji, 2011). The mature T cells undergo positive and negative selection, in which they are presented with self-antigens from the thymus for affinity selection to prevent autoreactive TCR repertoires. The gene rearrangement of a TCR involves the selection of immature T cells in the thymus maturing to become functional T cells that recognize foreign molecules and respond to them appropriately. TCR development in the thymus is critical for development of a functional immune system. The gene segment organization of the TCRγ and TCRδ chains is similar to that of the αβ TCR. The α chain is made up of the variable (V), joining (J) and constant (C) segments, and the β chain contains the V, D (diversity), J, and C segments. TCRs are heterodimeric membrane proteins that are composed of two chains, αβ or γδ. T cell function is initiated by recognition of a peptide antigen in a specific interaction via the T cell receptor (TCR) in the context of the major histocompatibility complex (MHC) expressed on antigen-presenting cells (APC). Furthermore, discussed here are bioinformatic tools that can be applied to study the structural biology of peptide/TCR/MHC (major histocompatibility complex) and predict antigenic epitopes using advanced artificial intelligence tools. This review provides an overview of the application and development of bulk RNA-seq and single-cell (SC) RNA-seq to examine the TCR repertoires. With the development of RNA technology, transcriptomic data must provide valuable information to model and predict TCR and antigen interaction and, more importantly, identify or predict neoantigens. RNA-seq (RNA sequencing) is a valuable tool for studying TCR repertoires by providing a comprehensive and quantitative analysis of the RNA transcripts. Understanding the specific TCR involved in this process can provide insights into the autoimmune process. The recognition of autologous peptides by adaptive immunity may lead to the development and progression of autoimmune diseases. Identifiers URN: urn:nbn:se:umu:diva-23195 DOI: 10.1182/blood-55 PubMedID: 12946997 OAI: oai:DiVA.T cell receptors (TCR) play a vital role in the immune system’s ability to recognize and respond to foreign antigens, relying on the highly polymorphic rearrangement of TCR genes. Place, publisher, year, edition, pages2003. In some cases the leukemic progenitor cell might arise earlier in lineage before DHJH recombination but retain the capacity to further differentiate into cells capable of altering the pattern of Ig and/or TCR rearrangements. MRD detection should include multiple gene targets to minimize false-negative samples or include also multicolor flow cytometry. Alteration of these clonal gene rearrangements is a common feature in childhood ALL. Using primers designed from the novel relapse sequences, the relapse clone could be identified as subdominant clones in the diagnostic sample in 8 of 14 patients. ![]() In 20% only new sequences were found at relapse. In 24%, one original sequence was preserved but the other lost, and in 14% the original sequences were conserved with new sequences identified at relapse. In 42%, all original Ig and/or TCR sequences were conserved. We analyzed the sequences of Ig and TCR gene rearrangements obtained at presentation and relapse in 41 children with ALL to study clonal stability, which has important implications for monitoring MRD, during the course of the disease. Immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements provide clonal markers useful for diagnosis and measurement of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL). 4520-4526 Article in journal (Refereed) Published Abstract
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