Rearrangement and expression of the T cell receptor (TCR) alpha chain is important for thymocyte development and initiation of thymic positive selection signaling. CD Genomics promotes the development of immunology, the study of disease mechanisms, and the development of novel therapies by providing expert α chain of TCR sequencing services.
The region of the α chain of the TCR furthest from the membrane is the variable (V) region, while the region closest to the membrane is the constant (C) region. The V and J gene regions recombine to form the V region exon of the α chain. Transcription of the V region and the C region exon together produces a primary RNA transcript. Splicing of this RNA produces an mRNA which, when translated, produces the TCR α chain protein.
Complementarity determining region 1 (CDR1) and CDR2, which are encoded in the TCR germline V gene, are conserved in α chain and β chain. In contrast to CDR1 and CDR2, CDR3 is located at the junction between the rearranged V and linkage (J) segments in the TCR α chain and between the V, diversity (D), and J segments in the TCR-β chain.
Fig.1 TCR α chain gene structure. (Clauze, A., et al., 2022)
Distinct from the β chain, the α chain genes of the TCR do not stop rearranging until the developing T cell undergoes positive selection. During the CD4+8+ 'double positive' (DP) stage of thymocyte development, both α chain alleles rearrange until they form a positively selectable heterodimer with the previously formed β chain, resulting in a Rag1/2 turn and stopping further rearrangement. Immature thymocytes (DP, TCRlo) frequently express a double α chain on the cell surface, but almost all mature (DP, or SP, TCRhi) thymocytes express a single α and β combination, which is known as phenotypic allelic exclusion.
Most peripheral T cells express a single α chain at the cell surface, although frequently (20-30%) there are two functionally rearranged and expressed α chain genes. Estimates of the number of peripheral T cells expressing both cell surface alpha chains vary widely, from less than 5% to 15% in mice, and can be as high as 30% in humans. Double receptor cells can cause autoimmunity in some systems, or have a high degree of alloreactivity, although other reports have not found them to increase susceptibility to autoimmunity. They have also been reported to effectively increase the reproducibility of the TCR.
Accurate characterization of all components of the TCR α and β chains is essential for understanding adaptive immunity, which has many applications in areas such as vaccine development and response, cancer clone tracking, and immunotherapy.
CD Genomics has a professional technical team and advanced equipment to provide efficient and reliable α chain of TCR sequencing services to our customers. A variety of library construction methods and top-notch sequencing technologies are used to meet the requirements of our customers. In addition, we have a professional bioinformatics team to provide our clients with data processing and analysis services.
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Multiple Library Construction Methods. |
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Advanced High-throughput Sequencing Platform. |
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Professional Data Analysis Team. |
As a pioneer in immunomics, CD Genomics has provided specialist TCR repertoire analysis to many research institutions over the years. Through collaborations with our clients, we promote the study of multiple disease mechanisms and the development of novel therapies. Please contact us for more information.
