In this regard, to comprehend the significance of the vast array of T cell clones identified and their relative quantitative relationship in the normal and disease states, a better understanding of the normal TCR repertoire features is needed. Nowadays, high-throughput TCR sequencing allows in-depth molecular analysis of T cell clones to get an unprecedented level of detail when examining the T cell repertoire of individuals. However, before the emerging of immune repertoire sequencing technology, the complexity and dynamics of the T-cell repertoire remain unknown because the potential repertoire size has made conventional sequence analysis intractable. The analysis of TCR usage, especially regarding CDR3 and the TRBV family, is currently an essential tool for deciphering mechanisms of autoimmunity, transplantation, cancer therapy, and infectious diseases. As CDR3 interacts most closely with the antigenic peptide, the diversity of CDR3 amino acid sequences provides a measure of T cell diversity in an antigen-selected T cell repertoire. Theoretically, a repertoire of approximately 10 18 different TCRs could be generated in humans. The antigen specificity of each TCR is largely determined by the CDR3 of the receptor beta chain, as it is generated by rearrangement of multiple V, D, and J gene segments, random trimming and addition of non-template nucleotides at the junction sites (N-diversity mechanisms) greatly increases its diversity further. Three hyper variable CDRs (CDR1, CDR2, CDR3) have been found in the variable regions of β-chain and α-chain. Mature T cells use the α/β heterodimeric TCR, which consists of 2 polypeptide chains (α and β), each containing one variable and one constant domain, to specific recognize the antigenic peptides in context with major histocompatibility complex (MHC) molecules. According to the type of TCR, T cells are classified into αβ T cells and γδ T cells, which both have been identified in the deciduas. The ability of the adaptive immune system to respond to any of the vast number of potential foreign antigens to which a person might be exposed relies on the highly polymorphic receptors expressed by B cells (immunoglobulins) and T cells (TCRs). Conclusions: Some repertoire features could be observed in the public sequences, highly abundance clones, and long TCR CDR3 sequences, which might be helpful for further study of immune behavior and immune response. Moreover, we identified that extensive N additions and increase of D gene usage contributing to TCR CDR3 length, and observed there was distinct usage frequency of amino acids in long CDR3 sequences compared to the short CDR3 sequences. Notably, there was skewed VDJ segment usage in long CDR3 sequences, the expression levels of 10 TRβV segments, 7 TRβJ segments and 2 TRβD segments were significantly different in the long CDR3 sequences compared to the short CDR3 sequences. Moreover, our studies provided evidence that public amino acid sequences are produced by multiple nucleotide sequences. Results: We found that public CDR3 sequences and high-frequency sequences had the same characteristics, both of them had fewer nucleotide additions and shorter CDR3 length, which were closer to the germline sequence. Methods: In this study, we used a combination of multiplex-PCR, Illumina sequencing and IMGT (ImMunoGeneTics)/HighV-QUEST for a standardized analysis of the repertoire features of TCR beta chain in the blood of healthy individuals, including the repertoire features of public TCR complementarity-determining regions (CDR3) sequences, highly expanded clones, long TCR CDR3 sequences. Assessment of the repertoire features of TCR is vital for us to deeper understand of immune behaviour and immune response. ![]() Background/Aims: To ward off a wide variety of pathogens, the human adaptive immune system harbors a vast array of T-cell receptors, collectively referred to as the TCR repertoire.
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