Regulation of pathogen-specific T cell immunity by SLAMF receptors

• Applicant: Dr. Verena van der Heide
• Subject Area: Anaesthesiology ; Immunology
• Term: from 2016 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 298950764

One of the hallmarks of adaptive immunity is the generation of pathogen-specific T cell populations. By virtue of their distinct T cell receptor (TCR), naïve T cells recognize microbial peptides displayed by antigen-presenting or infected cells in the context of the host's major histocompatibility complex (MHC) molecules. Once activated, these T cells undergo clonal expansion, mature to effector T cell subsets and eventually transition into long-lived memory T cells, which provide enhanced protection upon secondary infection. While TCR/MHC cross-linking is essential for the induction, the ultimate amplitude and quality of pathogen-specific T cell responses are shaped by signals from both co-stimulatory and inhibitory molecules. Signaling lymphocytic activation molecule family (SLAMF) members have recently gained attention as immunomodulatory co-receptors involved in optimal T cell activation and differentiation. Due to functional redundancy, however, the contribution of individual SLAMF receptors to the regulation of pathogen-specific T cell immunity is virtually unknown. In this proposal, we will employ established in vitro and in vivo models to systematically interrogate and define the kinetics of SLAMF receptors in the context of antigen-induced T cell immunity (Aim 1). Using a new immunodeficient mouse lacking all SLAMF receptors as a source for the construction of mixed bone marrow chimeras, we will be able to determine the overall impact of the SLAM family on pathogen-specific T cell immunity (Aim 2), and to define, through retrovirus-mediated reconstitution, the specific contribution of individual SLAMF receptors to the modulation of specific T cell responses (Aim 3). Our findings will provide both a better understanding of the role of SLAMF receptors in T cell-mediated control of infectious disease and help to identify potential targets for optimized or novel therapeutic interventions.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Dirk Homann