Zooming in on T-cell protection.

PURPOSE OF REVIEW: This review aims to deepen our appreciation of the intricate interactions underpinning CD8+ T-cell-mediated immunity to HIV-1, from the whole-cell level to the structure and function of signalling molecules driving diverse transcriptional programmes and differentiation states. RECENT FINDINGS: Unravelling the signals that trigger T-cell activation, elucidating the dynamic architecture of the immunological synapse, and comprehensive, high-resolution tissue cell atlases are transforming our understanding of T-cell biology during viral infections. SUMMARY: This review links multiple processes that together generate T-cell immunity with possible implications for vaccine development. It begins by examining the role of T-cell-mediated responses in protection against HIV-1 and the importance of targeting vulnerable epitopes on HIV-1 proteins to suppress viral replication. It then zooms in on the initiation of T-cell activation, differentiation, and effector functions, mediated by the formation of the immunological synapse, co-stimulatory signalling, and cytokine networks, which drive coordinated actions of multiple transcription factors and chromatin remodelling. It emphasizes the importance of T-cell diversity, the continuum of cellular differentiation states, tissue localization, and memory formation in shaping effective antiviral immunity.