Shorter TCR ?-Chains Are Highly Enriched During Thymic Selection and Antigen-Driven Selection.

ABSTRACT: The adaptive immune system uses several strategies to generate a repertoire of T cell receptors (TCR) with sufficient diversity to recognize the universe of potential pathogens. However, it remains unclear how differences in the T cell receptor (TCR) contribute to heterogeneity in T cell state. In this study, we used polychromatic flow cytometry to isolate highly pure CD4⁺/CD8⁺ naive and memory T cells, and applied deep sequencing to characterize corresponding TCR ?-chain (TCR?) complementary-determining region 3 (CDR3) repertoires. We find that shorter TCR? CDR3s with fewer insertions were highly enriched during thymic selection. Antigen-experienced T cells (memory T cells) harbor shorter CDR3s vs. naive T cells. Moreover, the public TCR? CDR3 clonotypes within cell subsets or interindividual tend to have shorter CDR3 length and a significantly larger size compared with "private" clonotypes. Taken together, shorter CDR3s highly enriched during thymic selection and antigen-driven selection, and further enriched in public T-cell responses. These results indicated that it may be evolutionary pressures drive short CDR3s to recognize most of antigen in nature.

SUBMITTER: Hou X 

PROVIDER: S-EPMC6399399 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature