Events

At this research seminar, Dr Olivier Lantz, Director, Clinical Immunology Laboratory at the Institut Curie, Paris Hospital (France) presents How do T-T interactions regulate the proliferation of CD4 T cells and maintain TCR diversity towards a nominal antigen?

About Dr Olivier Lantz

Dr Lantz received his MD and PhD from Paris Orsay University in 1986 and 1990, respectively. He studies the biology of innate like T cells (NKT and MAIT) and of CD4 T cells, as well as the interactions between the immune system and tumors. He discovered MAIT cells and performed their initial characterisation in several species. He demonstrated their anti-microbial reactivity restricted by MR1 and evidenced their abundance in human blood. He currently focuses on the development of MAIT cells and the analysis of their function in mouse models. He also studies the regulation of CD4 priming and acquisition of effector functions during primary immune responses.

Abstract

The way CD4 T cell proliferation is regulated after antigen (Ag) encounter is still badly known. For CD4 T cells, oligoclonality and avidity does not seem to increase much after repeated immunisations suggesting that active mechanisms are at play to prevent TCR repertoire narrowing. We previously showed that responding T cells specifically grab their cognate MHC:peptide complexes from the APCs. The captured MHC:peptide complexes prevent Ag-experienced T cells of the same specificity to proliferate allowing naïve T cells to be recruited into the response (1). We recently showed that simultaneous signaling by IFN-g and Il-2 induces SOCS1 activation leading to specific inhibition of Ag-experienced T cell proliferation (2).

Using Socs1 inactivation as a tool to disrupt the consequences of T-T interactions, we examined the diversity and characteristics of the TCR repertoire during an immune response. We studied the polyclonal response towards the I-Ab restricted Dby male Ag. scRNAseq VDJ analysis of I-Ab:Dby tetramer sorted CD4 T cells evidenced striking expansion of dominant clones in Socs1 KO cells as compared to the wt cells. The TCRs corresponding to the most expanded clones in wt and Socs1 KO cells were re-expressed in a reporter cell line. The avidity and the “promiscuity” of the most abundant TCRs from the Socs1 KO derived cells are compared to the wt counterparts.

In this talk, we will conclude by discussing our working model and the ongoing experiments examining upstream mechanisms and testing some of its prediction.