CD45RB Status of CD8⁺ T Cell Memory Defines T Cell Receptor Affinity and Persistence

The identity of CD45 isoforms on the T cell surface changes following the activation of naive T cells and impacts intracellular signaling. In this study, we find that the anti-viral memory CD8⁺ T pool is unexpectedly comprised of both CD45RB^hi and CD45RB^lo populations. Relative to CD45RB^lo memory T cells, CD45RB^hi memory T cells have lower affinity and display greater clonal diversity, as well as a persistent CD27^hi phenotype. The CD45RB^hi memory population displays a homeostatic survival advantage in vivo relative to CD45RB^lo memory, and long-lived high-affinity cells that persisted long term convert from CD45RB^lo to CD45RB^hi. Human CD45RO⁺ memory is comprised of both CD45RB^hi and CD45RB^lo populations with distinct phenotypes, and antigen-specific memory to two viruses is predominantly CD45RB^hi. These data demonstrate that CD45RB status is distinct from the conventional central/effector T cell memory classification and has potential utility for monitoring and characterizing pathogen-specific CD8⁺ T cell responses.