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Expansion of an Unusual Virtual Memory CD8⁺ Subpopulation Bearing Vα3.2 TCR in Themis-Deficient Mice.

ABSTRACT: Deletion of the gene for Themis affects T cell selection in the thymus, which would be expected to affect the TCR repertoire. We found an increased proportion of cells expressing Vα3.2 (TRAV9N-3) in the peripheral CD8⁺ T cell population in mice with germline Themis deficiency. Analysis of the TCRα repertoire indicated it was generally reduced in diversity in the absence of Themis, whereas the diversity of sequences using the TRAV9N-3 V-region element was increased. In wild type mice, Vα3.2⁺ cells showed higher CD5, CD6 and CD44 expression than non-Vα3-expressing cells, and this was more marked in cells from Themis-deficient mice. This suggested a virtual memory phenotype, as well as a stronger response to self-pMHC. The Vα3.2⁺ cells responded more strongly to IL-15, as well as showing bystander effector capability in a Listeria infection. Thus, the unusually large population of Vα3.2⁺ CD8⁺ T cells found in the periphery of Themis-deficient mice reflects not only altered thymic selection, but also allowed identification of a subset of bystander-competent cells that are also present in wild-type mice.

SUBMITTER: Prasad M

PROVIDER: S-EPMC8058184 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Altered thymic selection in Themis-deficient mice leads to expansion of an unusual virtual memory and bystander-competent CD8+ subpopulation bearing Va3.2 TCR

Project description:This study aimed to compare the TCRab repertoires from CD8 T cell subsets in a different T cell progression stage in Themis-sufficient and Themis-deficient mice. Analysis of the NGS-derived data revealed an overall reduction of the TCRa repertoire diversity in Themis's absence. In contrast, the CD8 compartment bearing the Va3.2 TCRs in the Themis-deficient model retains higher diversity than the repertoire from the Themis-sufficient counterpart. Furthermore, analysis of CDR3 peptide sequences of Va3.2+ and Va3.2- TCRs disclose the greater contribution of the hydrophobic residues in the former repertoires, indicating enhanced self-reactivity within this CD8+ T cell fraction.

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Altered thymic selection in Themis-deficient mice leads to expansion of an unusual virtual memory and bystander-competent CD8+ subpopulation bearing Va3.2 TCR

Project description:Altered thymic selection in Themis-deficient mice leads to expansion of an unusual virtual memory and bystander-competent CD8+ subpopulation bearing Va3.2 TCR

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THEMIS increases TCR signaling in CD4+CD8+ thymocytes by inhibiting the activity of the tyrosine phosphatase SHP1.

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