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Dr. Laurent Sabbagh

Assistant Professor
Research Center - Maisonneuve-Rosemont Hospital
Department of Microbiology and Immunology
University of Montreal

"Signalling lymphocyte survival through TRAF1"

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Abstract

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Tumour necrosis factor receptors (TNFRs) are a family of receptors involved in transmitting survival and death signals in lymphocytes. The balance between survival and death signalling plays a critical role in determining the outcome of an immune response and the subsequent survival and maintenance of memory T cells. TNFR-associated factors (TRAFs) are a family of adaptor proteins involved in linking TNFR family members to downstream signalling pathways. TRAF1 is unique among TRAFs in that it lacks a RING finger domain present in all other TRAFs and has the most restricted expression pattern; found almost exclusively in lymphocytes, dendritic cells and certain epithelia. Overexpression of TRAF1 in many tumours of B cell origin is consistent with a survival function. I will discuss the role of TRAF1 in the survival of CD8 memory T cells. In addition, the dependence of the 4-1BB receptor, a member of the TNFR family, on TRAF1 in mediating survival of CD8 T cells will be discussed. Using a systems biology approach novel TRAF1 binding partners have been identified to understand TRAF1-dependent-signalling pathways downstream of TNFRs in CD8 T cells. Understanding signalling events downstream of TNFRs and the contribution of TRAF1 will allow the design of new therapies to increase the output of CD8 memory T cells, enhancing not only cancer therapy regimens but infectious disease treatments as well.