![]() ![]() The TCR has to be specific to distinguish between self- and non-self-pMHC, but due to the large number of possible foreign antigens (> 20 9) a specific TCR is nevertheless expected to bind many different pMHC (i.e., cross-reactivity) ( Mason, 1998 Sewell, 2012). Most T cells express a single T-cell receptor (TCR) variant, which binds antigen in the form of a short peptide presented by the Major Histocompatibility Complex (pMHC) ( Davis and Bjorkman, 1988). The human adaptive immune system employs a vast number (> 10 11 ) of T lymphocytes, to detect and control pathogens. TCRα abundant sequences can be primarily attributed to many identical recombination events in different cells, while abundant TCRβ sequences are primarily derived from large clones, which make up a small percentage of the naive repertoire, and could be established early in the development of the T-cell repertoire. By combining experimental data with predictions from models we describe two mechanisms contributing to TCR sequence abundance. We detect abundant TCR sequences even after exclusion of methodological confounders such as sort contamination, and multiple mRNA sampling from the same cell. However, a substantial number of sequences were observed multiple times. We observe most TCR sequences only once, consistent with the enormous diversity of the repertoire. We estimated the abundance of TCR sequences in samples of naive T cells from blood using an accurate quantitative sequencing protocol. The clone size distribution of the human naive T-cell receptor (TCR) repertoire is an important determinant of adaptive immunity. ![]()
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