Biology subjects

Krovi, S. H.

Publications and source records attributed to Krovi, S. H..

2 recordsLinked to original sources

bioRxiv2020

Single-cell RNA transcriptomics identifies Hivep3 as essential in regulating the development of innate-like T lymphocytes

Most T lymphocytes leave the thymus as naive cells with limited functionality. However, unique populations of T cells, commonly known as innate-like T cells, differentiate into functionally distinct effector subsets during thymic development under the influence of the transcription factor PLZF. Here, we profiled >10,000 differentiating thymic iNKT cells using single-cell RNA sequencing to provide a comprehensive transcriptional landscape of their maturation, function, and fate decision in steady state. We identified Hivep3, a zinc finger transcription factor and adaptor protein, as a key factor that is expressed in early precursors and regulates the post-selection proliferative burst, differentiation and functions of iNKT cells. Importantly, we extended these results to other PLZF+ innate-like T cell populations, highlighting the unique and common requirement of Hivep3 to the development of all innate-like T cells.

immunology↗

bioRxiv2017

The somatically generated T cell receptor CDR3a contributes to the MHC allele specificity of the T cell receptor

Mature T cells bearing {beta} T cell receptors react with foreign antigens bound to alleles of major histocompatibility complex proteins (MHC) that they were exposed to during their development in the thymus, a phenomenon known as positive selection. The structural basis for positive selection has long been debated. Here, using mice expressing one of two different T cell receptor {beta} chains and various MHC alleles, we show that positive selection-induced MHC bias of T cell receptors is affected both by the germline encoded elements of the T cell receptor and {beta} chain and, surprisingly, dramatically affected by the non germ line encoded CDR3 of the T cell receptor chain. Thus, in addition to determining specificity for antigen, the non germline encoded elements of T cell receptors may help the proteins cope with the extremely polymorphic nature of major histocompatibility complex products within the species.

immunology↗