receptorrepertoire

The receptor repertoire refers to the entire set of antigen receptor sequences expressed by an individual’s B and T lymphocytes. It embodies the extraordinary diversity necessary to recognize the vast array of foreign antigens the immune system may encounter. This diversity arises through gene rearrangement processes that generate the variable regions of receptor chains, as well as additional diversification steps. In B cells, somatic hypermutation and class switch recombination further diversify receptors during immune responses. In T cells, repertoire diversity is shaped during development and by thymic selection.

The two main components are the B cell receptor (BCR) repertoire and the T cell receptor (TCR) repertoire. The BCR repertoire expands and mutates in germinal centers to optimize antigen binding, while the TCR repertoire develops in the thymus with selection for appropriate MHC recognition and self-tolerance. Both repertoires are molded by antigen exposure, infection, vaccination, age, and disease state, resulting in a dynamic landscape of clonotypes—groups of lymphocytes sharing a common receptor sequence.

Studying receptor repertoires relies on repertoire sequencing (Rep-Seq) of V(D)J regions, often coupled with single-cell approaches to preserve pairing information for heavy and light chains (in B cells) or alpha and beta chains (in T cells). Key metrics include clonotype richness, diversity indices (such as Shannon or Simpson), and measures of clonal expansion. The concept of public clonotypes refers to receptor sequences found in multiple individuals, reflecting convergent recombination or shared antigen experiences.

Applications span clinical and research contexts, including assessment of immune status, vaccine responses, infectious diseases, autoimmunity, and cancer immunotherapy. Repertoire analysis aids monitoring immune reconstitution, tracking minimal residual disease, and guiding immunogen design. Challenges remain, including sampling bias, sequencing errors, and the need for standardized analytical frameworks.