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Hoi Ming Li, Toyoko Hiroi, Yongqing Zhang, Alvin Shi, Guobing Chen, Supriyo De, E Jeffrey Metter, William H Wood, Alexei Sharov, Joshua D Milner, Kevin G Becker, Ming Zhan, Nan-ping Weng, TCRβ repertoire of CD4+ and CD8+ T cells is distinct in richness, distribution, and CDR3 amino acid composition, Journal of Leukocyte Biology, Volume 99, Issue 3, March 2016, Pages 505–513, https://doi.org/10.1189/jlb.6A0215-071RR
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Abstract
The TCR repertoire serves as a reservoir of TCRs for recognizing all potential pathogens. Two major types of T cells, CD4+ and CD8+, that use the same genetic elements and process to generate a functional TCR differ in their recognition of peptide bound to MHC class II and I, respectively. However, it is currently unclear to what extent the TCR repertoire of CD4+ and CD8+ T cells is different. Here, we report a comparative analysis of the TCRβ repertoires of CD4+ and CD8+ T cells by use of a 5′ rapid amplification of cDNA ends–PCR–sequencing method. We found that TCRβ richness of CD4+ T cells ranges from 1.2 to 9.8 × 104 and is approximately 5 times greater, on average, than that of CD8+ T cells in each study subject. Furthermore, there was little overlap in TCRβ sequences between CD4+ (0.3%) and CD8+ (1.3%) T cells. Further analysis showed that CD4+ and CD8+ T cells exhibited distinct preferences for certain amino acids in the CDR3, and this was confirmed further by a support vector machine classifier, suggesting that there are distinct and discernible differences between TCRβ CDR3 in CD4+ and CD8+ T cells. Finally, we identified 5–12% of the unique TCRβs that share an identical CDR3 with different variable genes. Together, our findings reveal the distinct features of the TCRβ repertoire between CD4+ and CD8+ T cells and could potentially be used to evaluate the competency of T cell immunity.