Related papers: Towards a quantitative theory of tolerance
Some cells have to take decision based on the quality of surroundings ligands, almost irrespective of their quantity, a problem we name "absolute discrimination". An example of absolute discrimination is recognition of not-self by immune T…
T cells are central to the adaptive immune response, capable of detecting pathogenic antigens while ignoring healthy tissues with remarkable specificity and sensitivity. Quantitatively understanding how T cell receptors (TCRs) discriminate…
Our main tenet argues that the primary role of positive thymic selection and the resulting T cell population is the maintenance of a homeostatic equilibrium with self MHC-self peptide complexes. The homeostatic T cell repertoire can…
The adaptive immune response relies on T cells that combine phenotypic specialization with diversity of T cell receptors (TCRs) to recognize a wide range of pathogens. TCRs are acquired and selected during T cell maturation in the thymus.…
We present a probabilistic T-cell model that includes negative selection and takes contrasting models of tissue-restricted antigen (TRA) expression in the thymus into account. We start from the basic model of van den Berg, Rand, and…
The phenomenon of oral tolerance refers to a local and systemic state of tolerance, induced in the gut associated lymphoid tissues, after its exposure to innocuous antigens, such as food proteins. While recent findings shed light in the…
A central question in human immunology is how a patient's repertoire of T cells impacts disease. Here, we introduce a method to infer the causal effects of T cell receptor (TCR) sequences on patient outcomes using observational TCR…
The human adaptive immune response is known to weaken in advanced age, resulting in increased severity of pathogen-born illness, poor vaccine efficacy, and a higher prevalence of cancer in the elderly. Age-related erosion of the T-cell…
Among various possible causes of autoimmune disease, an important role is played by infections that can result in a breakdown of immune tolerance, primarily through the mechanism of "molecular mimicry". In this paper we propose and analyse…
T cells orchestrate adaptive immune responses upon activation. T cell activation requires sufficiently strong binding of T cell receptors on their surface to short peptides derived from foreign proteins bound to protein products of the…
The immune system recognizes a myriad of invading pathogens and their toxic products. It does so with a finite repertoire of antibodies and T cell receptors. We here describe theories that quantify the immune system dynamics. We describe…
The efficient recognition of pathogens by the adaptive immune system relies on the diversity of receptors displayed at the surface of immune cells. T-cell receptor diversity results from an initial random DNA editing process, called VDJ…
The evolution of the adaptive immune system is characterized by changes in the relative abundances of the B- and T-cell clones that make up its repertoires. To fully capture this evolution, we need to describe the complex dynamics of the…
Following antigen stimulation, the net outcomes of a T cell response are shaped by integrated signals from both positive co-stimulatory and negative regulatory molecules. Recently, the blockade of negative regulatory molecules (i.e. immune…
Regulatory T cells (Tregs) play a crucial role in mediating immune response. Yet an algorithmic understanding of the role of Tregs in adaptive immunity remains lacking. Here, we present a biophysically realistic model of Treg mediated…
T lymphocytes (T cells) orchestrate adaptive immune responses upon activation. T cell activation requires sufficiently strong binding of T cell receptors (TCRs) on their surface to short peptides (p) derived from foreign proteins, which are…
Cytotoxic T lymphocytes eliminate infected or malignant cells, safeguarding surrounding tissues. Although experimental and systems-immunology studies have cataloged many molecular and cellular actors involved in an immune response, the…
It has been known for some time that human autoimmune diseases can be triggered by viral infections. Several possible mechanisms of interactions between a virus and immune system have been analysed, with a prevailing opinion being that the…
The adaptive immune system is a dynamical, self-organized multiscale system that protects vertebrates from both pathogens and internal irregularities, such as tumours. For these reason it fascinates physicists, yet the multitude of…
How does immune system evolve functional proteins - potent antibodies - in such a short time? We address this question using a microscopic, protein-level, sequence-based model of humoral immune response with explicitly defined interactions…