Sequencing and analysis of the human adaptive immune receptor repertoire

Adaptive immune cell populations (T cells and B cells) retain a molecular record of immune exposures, including infection and vaccination, in their specific antigen receptor repertoires. These receptor repertoires arise through V(D)J recombination, which assembles distinct combinations of germline-encoded V, D and J gene segments and introduces extensive junctional diversification to generate highly diverse antigen receptors that are subsequently shaped by developmental selection and antigen exposure. Recent advances in high-throughput sequencing enable adaptive immune receptor repertoires to be profiled at scale, across large cohorts and with increasing depth within individual samples. As a result, receptor repertoire profiling is emerging as a powerful approach for monitoring disease course and treatment responses in cancer, quantifying immune responses to infection and vaccination, and dissecting the immunological basis of inflammatory disease. In this Review, we discuss how human T cell and B cell receptor repertoires are formed, how inherited genetic variation shapes their architecture and how experimental and computational advances are enabling repertoire data to be translated into biological insight, clinical utility and repertoire-guided therapeutic opportunities.