Abstract
The adaptive immune system's capability to protect the body requires a highly diverse lymphocyte antigen receptor repertoire. However, the influence of individual genetic and epigenetic differences on these repertoires is not typically measured. By leveraging the unique characteristics of B, CD4+ T and CD8+ T-lymphocyte subsets from monozygotic twins, we quantify the impact of heritable factors on both the V(D)J recombination process and on thymic selection. We show that the resulting biases in both V(D)J usage and N/P addition lengths, which are found in naïve and antigen experienced cells, contribute to significant variation in the CDR3 region. Moreover, we show that the relative usage of V and J gene segments is chromosomally biased, with ∼1.5 times as many rearrangements originating from a single chromosome. These data refine our understanding of the heritable mechanisms affecting the repertoire, and show that biases are evident on a chromosome-wide level.
Highlights
The adaptive immune system’s capability to protect the body requires a highly diverse lymphocyte antigen receptor repertoire
Studies have shown that overall biases in gene segment usage are the product of a variety of mechanisms, including a preferred recombination between certain V and (D)J segments[2]; receptor selection based on binding affinity for different major histocompatibility complexes (MHCs; for T-cell receptor (TCR) rearrangements)[3,4]; and bias based on the distance between V, D and J segments (for immunoglobulin (Ig) rearrangements)[5]
We utilized the power of unique molecular identifiers (UMIs) and next-generation sequencing (NGS) to investigate the influence of heritable features on the lymphocyte receptor repertoire
Summary
The adaptive immune system’s capability to protect the body requires a highly diverse lymphocyte antigen receptor repertoire. A set of V (variable), D (diversity) and J (joining) gene segments are chosen from the genetically encoded repertoire to create a typically unique receptor for each B and T cell This process is known as V(D)J recombination[1]. Recent studies have shown that the naıve and memory repertoires within an individual are highly correlated, and that activation of naıve cells and subsequent transition of those cells to the memory population does not appear to be dependent on V gene usage[11,12] These studies hypothesize that genetically determined biases in the naıve repertoire will be propagated to the memory compartment, this has not been clearly demonstrated. Determining the influence of genetics on the memory compartment is important for understanding the relationship between the naıve and memory subsets and, more generally, how genetics affects response to infection
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
