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

Abstract

The identity of CD45 isoforms on the Tcell surface changes following the activation of naive Tcells and impacts intracellular signaling. In this study, we find that the anti-viral memory CD8+ T pool is unexpectedly comprised of both CD45RBhi and CD45RBlo populations. Relative to CD45RBlo memory Tcells, CD45RBhi memory Tcells have lower affinity and display greater clonal diversity, as well as a persistent CD27hi phenotype. The CD45RBhi memory population displays a homeostatic survival advantage invivo relative to CD45RBlo memory, and long-lived high-affinity cells that persisted long term convert from CD45RBlo to CD45RBhi. Human CD45RO+ memory is comprised of both CD45RBhi and CD45RBlo populations with distinct phenotypes, and antigen-specific memory to two viruses is predominantly CD45RBhi. These data demonstrate that CD45RB status is distinct from the conventional central/effector Tcell memory classification and has potential utility for monitoring and characterizing pathogen-specific CD8+ Tcell responses.