Related papers: How heterogeneous thymic output and homeostatic pr…
Naive human T cells are produced in the thymus, which atrophies abruptly and severely in response to physical or psychological stress. To understand how an instance of stress affects the size and "diversity" of the peripheral naive T cell…
The ability of the adaptive immune system to respond to arbitrary pathogens stems from the broad diversity of immune cell surface receptors (TCRs). This diversity originates in a stochastic DNA editing process (VDJ recombination) that acts…
Diverse T and B cell repertoires play an important role in mounting effective immune responses against a wide range of pathogens and malignant cells. The number of unique T and B cell clones is characterized by T and B cell receptors (TCRs…
An essential feature of the adaptive immune system is the proliferation of antigen-specific lymphocytes during an immune reaction to form a large pool of effector cells. This proliferation must be regulated to ensure an effective response…
The diversity of T-cell receptors recognizing foreign pathogens is generated through a highly stochastic recombination process, making the independent production of the same sequence rare. Yet unrelated individuals do share receptors, which…
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.…
The adaptive immune system responds to pathogens by selecting clones of cells with specific receptors. While clonal selection in response to particular antigens has been studied in detail, it is unknown how a lifetime of exposures to many…
The adaptive immune system relies on the diversity of receptors expressed on the surface of B and T-cells to protect the organism from a vast amount of pathogenic threats. The proliferation and degradation dynamics of different cell types…
T cell receptors (TCRs) bind foreign or self-peptides attached to major histocompatibility complex (MHC) molecules, and the strength of this interaction determines T cell activation. Optimizing the ability of T cells to recognize a…
The T-cell (TCR) repertoire relies on the diversity of receptors composed of two chains, called $\alpha$ and $\beta$, to recognize pathogens. Using results of high throughput sequencing and computational chain-pairing experiments of human…
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…
Each T cell typically carries a specific T-cell receptor (TCR) that determines its specificity against an epitope presented by the HLA complex on a target cell. Antigenic challenge triggers the expansion of reactive cells within a diverse…
The clonal expansion of T cells during an infection is tightly regulated to ensure an appropriate immune response against invading pathogens. Although experiments have mapped the trajectory from expansion to contraction, the interplay…
The diversity of T-cell receptor (TCR) repertoires is achieved by a combination of two intrinsically stochastic steps: random receptor generation by VDJ recombination, and selection based on the recognition of random self-peptides presented…
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 human T cell repertoire is generated by the rearrangement of variable (V), diversity (D) and joining (J) segments on the T cell receptor (TCR) loci. To determine whether the structural ordering of these gene segments on the TCR loci…
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…
A key challenge in molecular biology is to decipher the mapping of protein sequence to function. To perform this mapping requires the identification of sequence features most informative about function. Here, we quantify the amount of…
T-cell receptors (TCR) are key proteins of the adaptive immune system, generated randomly in each individual, whose diversity underlies our ability to recognize infections and malignancies. Modeling the distribution of TCR sequences is of…
Examination of T-cell receptor (TCR) clonality has become a way of understanding immunologic response to cancer and its interventions in recent years. An aspect of these analyses is determining which receptors expand or contract…