TCRβ repertoire of CD4+ and CD8+ T cells is distinct in richness, distribution, and CDR3 amino acid composition

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

Research output: Contribution to journalArticle

15 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)505-513
Number of pages9
JournalJournal of Leukocyte Biology
Volume99
Issue number3
DOIs
StatePublished - Mar 2016

Keywords

  • Human
  • RACE
  • RNAseq
  • Supervised learning
  • TCR diversity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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