Related papers: Quantifying selection in immune receptor repertoir…
To recognize pathogens, B and T lymphocytes are endowed with a wide repertoire of receptors generated stochastically by V(D)J recombination. Measuring and estimating the diversity of these receptors is of great importance for understanding…
Stochastic rearrangement of germline DNA by VDJ recombination is at the origin of immune system diversity. This process is implemented via a series of stochastic molecular events involving gene choices and random nucleotide insertions…
We quantify the VDJ recombination and somatic hypermutation processes in human B-cells using probabilistic inference methods on high-throughput DNA sequence repertoires of human B-cell receptor heavy chains. Our analysis captures the…
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…
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…
The diversity of the immune repertoire is initially generated by random rearrangements of the receptor gene during early T and B cell development. Rearrangement scenarios are composed of random events -- choices of gene templates, base pair…
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 antibody repertoire of each individual is continuously updated by the evolutionary process of B cell receptor mutation and selection. It has recently become possible to gain detailed information concerning this process through…
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…
With the advent of high-throughput sequencing technologies, the fields of immunogenomics and adaptive immune receptor repertoire research are facing both opportunities and challenges. Adaptive immune receptor repertoire sequencing…
Subclasses of lymphocytes carry different functional roles to work together to produce an immune response and lasting immunity. Additionally to these functional roles, T and B-cell lymphocytes rely on the diversity of their receptor chains…
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…
The evolutionary dynamics of HIV during the chronic phase of infection is driven by the host immune response and by selective pressures exerted through drug treatment. To understand and model the evolution of HIV quantitatively, the…
Cell functional diversity is a significant determinant on how biological processes unfold. Most accounts of diversity involve a search for sequence or expression differences. Perhaps there are more subtle mechanisms at work. Using the…
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 repertoire of lymphocyte receptors in the adaptive immune system protects organisms from diverse pathogens. A well-adapted repertoire should be tuned to the pathogenic environment to reduce the cost of infections. We develop a general…
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…
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…
During chronic infection, HIV-1 engages in a rapid coevolutionary arms race with the host's adaptive immune system. While it is clear that HIV exerts strong selection on the adaptive immune system, the characteristics of the somatic…
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…