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L-Leucyl-L-Leucine methyl ester (LLME) is a lysosomal condensation product that has been reported to be cytotoxic towards natural killer cells and CD4+ and CD8+ T lymphocytes without affecting helper T cells and B cells. [1] [2] It has also been shown to induce death of monocytes, polymorphonuclear leukocytes, and myeloid tumor cells. [2] Upon entry into cells via receptor-mediated endocytosis, LLME undergoes a condensation process catalyzed by dipeptidyl peptidase I (DPPI) in lysosomes. This condensation leads to lysosomal rupture and DNA fragmentation in DPPI-expressing immune cells such as cytotoxic T cells and natural killer cells. [2]

Reference:

[1]. Ohlin, M., Danielsson, L., Carlsson, R., et al. The effect of leucyl-leucine methyl ester on proliferation and Ig secretion of EBV-transformed human B lymphocytes. Immunology 66(4), 485-490 (1989).

[2]. Thiele, D.L., and Lipsky, P.E. Mechanism of L-leucyl-L-leucine methyl ester-mediated killing of cytotoxic lymphocytes: Dependence on a lysosomal thiol protease, dipeptidyl peptidase I, that is enriched in these cells. Proceedings of the National Academy of Sciences of the United States of America 87(1), 83-87 (1990).