Abstract When T-cell clones were first grown in long-term cell culture, each clone was considered to be capable of displaying a limited range of functional activities, constrained by the clones’ coreceptor, CD4 or CD8, and the specificity of its antigen-specific receptor (TCR) for one or a few peptides in association with a class I or class II MHC molecule. Subsequent studies, especially with transgenic mice, have shown, however, that T cells expressing the same receptor can be obtained in a variety of differentiated states, including naïve cells, activated effector cells, memory cells, and anergic or tolerant cells, as well as cells with or without a coreceptor. In each of these states T cells can display distinctly different responses to the peptide-MHC (pepMHC) complexes the TCR recognizes. Recently, memory T cells have received considerable attention, in part because of the likelihood that they confer long-term protective immunity against diverse infectious agents and possibly against some forms of cancer. Here we review some recent studies that our colleagues and we have carried out on memory CD8 + T cells. These studies have made extensive use of cells that express the TCR called 2C. The diverse set of cells expressing the 2C TCR, in mice and in cultured clones and cell lines, are referred to as the 2C system. Before reviewing the studies of memory cells, we summarize the 2C system’s main features, including evidence that a large and diverse array of pepMHC complexes, involving at least four class I MHC proteins, can stimulate TCR-mediated responses of 2C cells.