# UBL3 Participates in the Early Stages of CD83‐Dependent CD4+ T Cell Selection

## TL;DR

This study shows that UBL3 helps regulate MHC II on thymic cells and influences early CD4+ T cell selection, especially when CD83 is missing.

## Contribution

The novel finding is that UBL3 contributes to CD4+ T cell selection by regulating MHC II in the absence of CD83.

## Key findings

- UBL3 deletion in CD83-deficient mice increases surface MHC II on thymic epithelial cells.
- UBL3 influences the CD4+ CD8low CD69+ stage of positive selection in CD83-deficient mice.
- The role of UBL3 in CD4+ T cell selection is limited to early developmental stages.

## Abstract

CD83 is critical for CD4+ T cell selection. It regulates MHC II ubiquitination and turnover at the surface of thymic epithelial cells (TECs). The role of UBL3, a recently identified adaptor molecule for MHC II ubiquitination, is unknown in thymic selection. Here we demonstrate that UBL3 regulates MHC II in TECs and participates in CD4+ T cell selection. Deleting UBL3 in CD83 loss‐of‐function mice (Cd83anu/anu Ubl3−/−
) increases MHC II on the surface of Cd83anu/anu
TECs. This increase in surface MHC II correlates with increased positive selection of CD4+ T cells. Analysis of Cd83anu/anu
and Cd83anu/anu Ubl3−/−
mice identifies the CD4+ CD8low CD69+ stage of positive selection as the origin of the CD4+ T cell selection defect in Cd83anu/anu
mice. This stage of CD4+ T cell positive selection is also impacted by UBL3. The positive selection defect in the absence of CD83 also manifests as alterations in CCR7+ CD4 single‐positive (SP) thymocytes. At the later stages of CD4+ T cell development, a role for UBL3 is no longer detected. In summary, through in‐depth phenotyping of thymocyte populations, a role for CD83 and UBL3 in regulating the early stages of CD4+ T cell positive selection has been identified.

CD83 and UBL3 are regulators of MHCII surface expression; however, only CD83 has a known role in regulating CD4+ T cell selection. This paper describes a role for UBL3 in regulating MHC II expression on thymic epithelium in a CD83‐deficient context, leading to alterations in CD4+ T cell positive selection.