7/22/2023 0 Comments Dna vs rna tcr repertoireBeta genes incorporate an additional D region minigene between V and J, giving rise to two junctions (not shown). Both alpha and beta genes undergo recombination independently. During recombination base pairs can be removed and/or added at the junction before the final ligation ( A). Individual V and J genes are selected stochastically (but not uniformly) and recombined during T-cell development in the thymus. T-cell recombination and the generation of diversity. ![]() This prevented a global analysis of the full repertoire of B- or T-cell antigen receptors using conventional DNA sequencing. This system produces an enormous diversity of receptor sequences, and each biological sample of blood or tissue will typically have thousands or millions of receptors. The combinatorial diversity generated by there being multiple V, J and (in certain chains) D genes to ‘choose’ from is hugely augmented by non-templated nucleotide additions and deletions occurring at the junctions of the segments, during the joining process. Recombination of the genomic DNA during lymphocyte development results in the physical joining of one of each available type of gene segment, and excision of the intervening DNA. In brief, the locus encoding each chain is comprised of multiple gene segments (‘minigenes’), which include V, D and J genes. see reviews, and diagrammatic illustration in Figure 1). The mechanism for the generation of variable antigen receptor diversity has been studied in great detail (e.g. The adaptive immune system of jawed vertebrates uses imprecise somatic DNA recombination to generate a rich and diverse array of antigen-specific receptors on B cells (BCR) and T-cells (TCR). T-cell receptor, high-throughput sequencing, immune repertoire, somatic recombination, generation of diversity, personalized biomarkers Introduction Computational analysis will provide the key to unlock the potential of the T-cell receptor repertoire to give insight into the fundamental biology of the adaptive immune system and to provide powerful biomarkers of disease. ![]() Sophisticated machine learning algorithms are being developed that can combine the paradoxical degeneracy and cross-reactivity of individual T-cell receptors with the specificity of the overall T-cell immune response. Finally, we discuss the major challenge of linking T-cell receptor sequence to function, and specifically to antigen recognition. High-level processing can measure the diversity of the repertoire in different samples, quantify V and J usage and identify private and public T-cell receptors. The latest generation of bioinformatics tools allows millions of DNA sequences to be accurately and rapidly assigned to their respective variable V and J gene segments, and to reconstruct an almost error-free representation of the non-templated additions and deletions that occur. We outline the major steps in processing of repertoire data, considering low-level processing of raw sequence files and high-level algorithms, which seek to extract biological or pathological information. However, the extraordinary heterogeneity of the immune repertoire poses significant challenges for subsequent analysis of the data. Massively parallel high-throughput sequencing allows millions of different T-cell receptor genes to be characterized from a single sample of blood or tissue. T-cell specificity is determined by the T-cell receptor, a heterodimeric protein coded for by an extremely diverse set of genes produced by imprecise somatic gene recombination.
0 Comments
Leave a Reply. |