Most memory phenotype (MP) CD44^hi CD8⁺ cells are resting interleukin (IL)-15–dependent cells characterized by high expression of the IL-2/IL-15 receptor β (CD122). However, some MP CD8⁺ cells have a CD122^lo phenotype and are IL-15 independent. Here, evidence is presented that the CD122^lo subset of MP CD8⁺ cells is controlled largely by major histocompatibility complex (MHC) class I molecules. Many of these cells display surface markers typical of recently activated T cells (CD62L^lo, CD69^hi, CD43^hi, and CD127^lo) and show a high rate of background proliferation. Cells with this phenotype are highly enriched in common γ chain–deficient mice and absent from MHC-I^−/− mice. Unlike CD122^hi CD8⁺ cells, CD122^lo MP CD8⁺ cells survive poorly after transfer to MHC-I^−/− hosts and cease to proliferate. Although distinctly different from typical antigen-specific memory cells, CD122^lo MP CD8⁺ cells closely resemble the antigen-dependent memory CD8⁺ cells found in chronic viral infections.