Building immunoglobulin and T cell receptor gene databases for the future

Abstract

Genetic databases for immunoglobulin (IG) and T cell receptor (TR) genes have evolved from small catalogs to critical resources underpinning immunogenetic research. Accurate annotation enables the analysis of repertoire diversity, somatic hypermutation, clonal relationships, and lineage development. Recent advances in high-throughput repertoire sequencing and long-read genomics now allow for unprecedented discovery of germline variation across populations and species, but they also expose limitations of existing resources. Here, we discuss the historical evolution of IG/TR databases, highlight the challenges and opportunities presented by changing data landscapes, and outline strategies for building future databases that integrate genomic and expression data, support population diversity, and align with evolving nomenclature frameworks. Enhanced germline resources will be essential for accurate annotation, reproducible research, and the next generation of immunological discovery and clinical translation.