The Ly-6 family of glycosylphosphatidylinisotol proteins is excellent differentiation markers of immune cells during their development and they regulate signaling responses. Specifically, Ly-6A is up-regulated on a variety of transformed cells therefore making it a potential biomarker for cancer detection and therapy. Previous work in our laboratory revealed that a transformed CD4+ T lymphocyte cell line shows growth inhibition and apoptotic cell death when Ly-6A proteins are engaged. We have investigated whether this mechanism involves p53 protein, which is known to regulate the cell cycle, trigger growth inhibition and apoptotic cell death in several normal cell types. In cancer cells, p53 is often mutated, resulting in uncontrollable cell growth. The cell cycle is regulated by several proteins known as cyclin dependent kinases that bind cyclin proteins and usher the cell past checkpoints in the cell cycle. Therefore, we have examined the expression of relevant cell cycle and apoptotic proteins. We find that while growth inhibition and cell death in the T cell line was p53 independent, the cell cycle inhibitor gene p27 becomes significantly up-regulated. Furthermore, we extended this study beyond the analysis of one Ly-6A antibody and one T-cell line. We find that the responses were tied primarily to the extent of cross-linking with anti-Ly-6A antibody. Other transformed T-cell lines also exhibited growth inhibition and cellular death when the Ly-6A protein was engaged.