Anti-THEMIS monoclonal antibody, clone FQS8465

We propose Themis, a bot detection approach based on the inference of the structure of time varying IP-to-IP communication with the Stochastic Block Model (SBM). Themis uses the inferred structure to detect and quantify abnormal behavior of individual hosts. The novelty of our approach is the use of probabilistic inference directly on host interactions to model normality. The challenges of our approach are the adaptation of the inference process to obtain usable outputs in a dynamic system, and the specification of abnormal behavior with respect to the inferred structure. Themis identifies infected hosts with accuracy larger 95 % and compares favorably against state of the art botnet detection mechanisms.

T cell homeostasis and functional responsiveness require signals from self-peptide-major histocompatibility complex (self-pMHC) and cytokines, but the mechanisms controlling this signal integration are unknown. Using a conditional deletion of the T cell lineage-specific protein Themis, we show that Themis is required for the maintenance of peripheral CD8(+) T cells and for proliferative CD8(+) T cell responses to low-affinity pMHC aided by cytokines. Themis-deficient peripheral T cells show a phenotype indicative of reduced tonic signaling from self-pMHC, strongly suggesting that Themis is a positive regulator of T cell receptor signal strength in response to low-affinity self-pMHC in peripheral T cells. Signals from low-affinity pMHC and cytokines synergistically induce phosphorylation of the kinase Akt, metabolic changes and c-Myc transcription factor induction in CD8(+) T cells only in the presence of Themis. This function of Themis is mediated through Shp1 phosphatase, as peripheral Themis and Shp1 double deletion rescues the peripheral CD8(+) T cell maintenance. T cell homeostasis requires integration of signals from antigen and cytokine receptors. Gascoigne and colleagues demonstrate that the protein Themis supports signals from low-affinity TCR ligands to maintain normal CD8(+) cell function.