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Kanupriya Kusumaker, MBBS, MD, MMSc




Research Fellow




Research Fellow




Kanupriya Kusumakar* , Elodie Macho-Fernandez, Nimisha Schneider, David Sweezy, Rebecca Mirochnik, Natasha Veerapen, Gurdyal Besra, Laurent Gapin, Manfred Brigl

Distinct roles of antigen-presenting cells in activation of mucosal-associated invariant T-cells

Participation in the Women in Medicine & Science Symposium will give me the chance to connect with fellow women scientists and get inspired by their work. Such events give us a brilliant platform to share, learn and motivate each other. Also, promoting women scientists is essential to overcome various hurdles we face in this field.

My research/ clinical interests include exploring the MAIT cell biology in the context of intestinal immunity, antimicrobial resistance and rapid diagnostics for infectious diseases.

Background: Mucosal-Associated Invariant T-cells (MAIT cells) are innate T-cells that recognize microbial antigens presented by MHC class I-related (MR1) molecules. Despite ubiquitous expression of MR1 and recent breakthroughs in understanding MAIT cell biology, the antigen presenting cells (APCs) that drive MAIT cell activation remain poorly characterized.

Methods: Using different in-vitro and in-vivo models, we provide a comprehensive analysis of the role of different APCs in MAIT cell activation.

Results: Dendritic cells (DCs) and macrophages efficiently present antigens to MAIT cells, while  B-cells do not. Additionally, stimulation of MAIT cells with antigen-loaded DCs resulted in greater proliferation of MAIT cells compared to macrophages. Moreover, higher cytokine secretion was noted in combined TLR/antigen stimulation in DC/T-cell co-cultures compared to stimulation with antigen or TLR alone. While only a modest increase was noted in similar macrophage/T-cell co-cultures. Notably, depletion of DCs/macrophages caused reduction in MAIT cell expansion, but depletion of B-cells had an opposite effect. Furthermore, adoptive transfer ofantigen-loaded BMDCs/BMDMs into wild-type mice recapitulated our in-vitro findings.

Conclusions: Various APCs differ in their abilities to activate MAIT cells with DCs being most potent. These findings suggest that APC- targeted approaches to MAIT cell activation may open novel avenues for therapeutic manipulation of MAIT cells.