Immunoreceptors have crucial roles in sensing environmental signals and initiating immune responses to protect the host. Dysregulation of immunoreceptor signalling can therefore lead to a range of diseases, making immunoreceptor-based therapies a promising frontier in biomedicine. A common feature of various immunoreceptors is the basic-residue-rich sequence (BRS), which is a largely unexplored aspect of immunoreceptor signalling. The BRS is typically located in the cytoplasmic juxtamembrane region of immunoreceptors, where it forms dynamic interactions with neighbouring charged molecules to regulate signalling. Loss or gain of the basic residues in an immunoreceptor BRS has been linked to severe human diseases, such as immunodeficiency and autoimmunity. In this Perspective, we describe the role of BRSs in various immunoreceptors, elucidating their signalling mechanisms and biological functions. Furthermore, we highlight pathogenic mutations in immunoreceptor BRSs and discuss the potential of leveraging BRS signalling in engineered T cell-based therapies.

免疫受体在感应环境信号和启动免疫反应以保护宿主方面起着至关重要的作用。因此，免疫受体信号的失调会导致一系列疾病，使基于免疫受体的疗法成为生物医学的一个有前途的前沿领域。各种免疫受体的一个共同特征是富含碱基残基的序列 （BRS），这是免疫受体信号转导的一个基本未被探索的方面。BRS 通常位于免疫受体的细胞质近膜区域，在那里它与邻近的带电分子形成动态相互作用以调节信号传导。免疫受体 BRS 中碱性残基的丢失或增加与严重的人类疾病有关，例如免疫缺陷和自身免疫。在这个观点中，我们描述了 BRS 在各种免疫受体中的作用，阐明了它们的信号传导机制和生物学功能。此外，我们强调了免疫受体 BRS 中的致病性突变，并讨论了在基于 T 细胞的工程疗法中利用 BRS 信号传导的潜力。