T cell receptor CDR3 loop length repertoire is determined primarily by features of the V(D)J recombination reaction.
ABSTRACT The third complementarity-determining region (CDR) of the TCR alpha and beta chains forms loops that engage amino acid residues of peptides complexed with MHC. This interaction is central to the specific discrimination of antigenic-peptide-MHC complexes by the TCR. The TCRbeta chain CDR3 loop is encoded by the Dbeta gene segment and flanking portions of the Vbeta and Jbeta gene segments. The joining of these gene segments is imprecise, leading to significant variability in the TCRbeta chain CDR3 loop length and amino acid composition. In marked contrast to other pairing antigen-receptor chains, the TCR beta and alpha chain CDR3 loop size distributions are relatively narrow and closely matched. Thus, pairing of TCR alpha and beta chains with relatively similar CDR3 loop sizes may be important for generating a functional repertoire of alpha beta TCR. Here we show that the TCRbeta chain CDR3 loop size distribution is minimally impacted by TCRbeta chain or alpha beta TCR selection during thymocyte development. Rather, this distribution is determined primarily at the level of variable-region gene assembly, and is critically dependent on unique features of the V(D)J recombination reaction that ensure Dbeta gene segment utilization.
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ABSTRACT: Historically, sharing T cell receptors (TCRs) between individuals has been speculated to be impossible, considering the dramatic discrepancy between the potential enormity of the TCR repertoire and the limited number of T cells generated in each individual. However, public T cell response, in which multiple individuals share identical TCRs in responding to a same antigenic epitope, has been extensively observed in a variety of immune responses across many species. Public T cell responses enable individuals within a population to generate similar antigen-specific TCRs against certain ubiquitous pathogens, leading to favorable biological outcomes. However, the relatively concentrated feature of TCR repertoire may limit T cell response in a population to some other pathogens. It could be a great benefit for human health if public T cell responses can be manipulated. Therefore, the mechanistic insight of public TCR generation is important to know. Recently, high-throughput DNA sequencing has revolutionized the study of immune receptor repertoires, which allows a much better understanding of the factors that determine the overlap of TCR repertoire among individuals. Here, we summarize the current knowledge on public T-cell response and discuss future challenges in this field.Cell Research 01/2012; 22(1):33-42. · 11.98 Impact Factor
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ABSTRACT: Problem statement: More and more severe hepatitis cases reported in China are infected with HBV and the immune response of HBV will be reduced if mutations occur in the TCR, therefore it is very important to investigate the relation of T-cellular function and clinical effect by studying the function of T-cell receptor. Approach: Artificial Neural Networks (ANN) was applied to analyze basic data (the three structural of HBsAg, the ligand of HBsAg and the clinical immunological characterizations, the laboratory data, the genetypes of cationic trypsinogen gene (PRSS1) derived from 78 patients with pancreatitis and 60 normal controls were also collected. What is more, we used T-cell culture with HBV and flow cytometry to check the result of ANN predict. To examine the characteristics of T-cells capable of coexisting with the secreted HBsAg, T-cell receptor from A121T, C139S, silent mutation and normal PRSS1 gene in the patients with pancreatitis were put into research. To ensure that PRSS1 gene would affect HBsAg-specific T-cells receptor, we compared the rate of multiplication and CD4/CD8 of T-cell after culture with HBV at 0H, 12H, 24H, 36H, 48H and 72H time point. Results: The protein’s structural predicted by the ANN could specifically explain the phenomenon that the turbulence and different of anti-HBs lever of the patients with pancreatitis. The three-dimensional of the protein that consist with PRSS1 gene would accord with HBsAg. It may be one of the HBsAg-specific T-cell receptor. Result of T-cell culture also showed that different genetypes of PRSS1 had different results. In the T-cell proliferation, the groups of PRSS1 mutation (A121T and C139S) were significant lower than the group of silent mutation and normal controls and it was the same to the result of CD4/CD8. Conclusion: The ANN had been integrated into a previously published comprehensive web server to support immunology analysis and the PRSS1 gene may be the unit for HBsAg immune response.American Journal of Immunology. 01/2009;
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ABSTRACT: V(D)J recombination assembles antigen receptor genes from germline V, D and J segments during lymphocyte development. In αβT-cells, this leads to the subsequent expression of T-cell receptor (TCR) β and α chains. Generally, V(D)J recombination is closely controlled at various levels, including cell-type and cell-stage specificities, order of locus/gene segment recombination, and allele usage to mediate allelic exclusion. Many of these controls rely on the modulation of gene accessibility to the recombination machinery, involving not only biochemical changes in chromatin arrangement and structural modifications of chromosomal organization and positioning, but also the refined composition of the recombinase targets, the so-called recombination signal sequences. Here, we summarize current knowledge regarding the regulation of V(D)J recombination at the Tcrb gene locus, certainly one for which these various levels of control and regulatory components have been most extensively investigated.Seminars in Immunology 12/2010; 22(6):330-6. · 5.93 Impact Factor