CD45RB Status Defines TCR Priming Affinity and CD8(+) T Cell Memory Persistence

Abstract T cell receptor (TCR) affinity plays a critical role in shaping T cell differentiation, but few studies have investigated the role of TCR affinity in the context of the endogenous CD8+ T cell memory pool. While naïve CD8+ T cells express primarily large CD45 isoforms (denoted as CD45RBhi), CD8+ T cell memory cells are traditionally described as expressing small isoforms (CD45RBlo). Interestingly, although CD8+ T cell memory to acute infection with LCMV included CD45RBlo cells, we found that over half of the CD8+ T cell memory pool remained CD45RBhi. The 2D micropipette affinity assay revealed that CD45RBhi memory cells had a 29-fold lower affinity for antigen relative to CD45RBlo cells. CD45RBloand CD45RBhi memory cells expressed similar levels of granzyme B and IFN-γ, but RNASeq analysis revealed that these populations differentially expressed over 150 genes. Phenotypically, the CD45RBhi population contained a higher frequency of the CD62LhiCD27hiCD127hiKLRG1lo persistent memory phenotype compared to CD45RBlo cells. We found that from early to late memory time-points, portions of each of the CD45RBhi and CD45RBlo populations underwent conversion to CD62Lhi, demonstrating that CD45RB status is distinct from the TCM phenotype. Adoptive transfer of purified CD45RBhi and CD45RBlo populations into naïve mice revealed that CD45RBlo memory cells underwent significant cell loss relative to CD45RBhi memory cells. Over time, the majority of CD45RBlo cells homeostatically converted to the CD45RBhipersistent memory phenotype. Together, these data demonstrate a novel role for CD45RB expression as a marker of TCR priming affinity, and describe a novel way in which CD45RB status can functionally categorize the CD8+ T cell memory pool.