Targeting dendritic cell plasticity to modulate antigen-specific T cell recall responses in human

The human immune system has the ability to fight various infectious diseases or self-cells turning malignant.

Dendritic cells (DCs) are innate immune sensors and professional antigen presenting cells that initiate the development of adaptive immune responses towards the formation of memory cells. Very important studies deciphered the various signals in DCs to effectively polarize naïve T cells.

However, a significant gap of knowledge remains on how DCs can mediate and influence antigen-specific T cell recall responses.In this program, we aim to investigate how the different human DC subsets can modulate antigen-specific T cell recall responses directed against influenza (Flu) epitopes.

To this end, we have designed a set of highly integrated work packages:WP1: Using a systematic experimental approach of challenging co-cultures of pure DCs (6 different subsets) and Flu-specific T cells from healthy subjects, we will generate a functional atlas revealing the impact of the different DC subsets on antigen-specific T cell recall responses.

T cell response status will be assessed at the protein level using phenotypic and functional approaches on multimer positive T cells.WP2: Using CITE-seq technology together with cutting-edge system biology platforms, we will interrogate the transcriptomic programs and molecular pathways associated with antigen-specific T cell recall responses following stimulation with the various DC subsets.WP3: As a complementary analysis of the data generated in WP2, we will perform TCR repertoire analysis to compare the clonal composition of the responding antigen-specific T cells.This program represents an ambitious and promising project that will generate novel biological insights into fundamental immunological mechanisms of human DC-T cell communication.

Such information could have direct clinical impact on the design of therapeutic DC-based vaccines, immunotherapies targeting DCs or T cell expansion protocols for adoptive transfer therapy