A novel intracellular pool of LFA-1 is critical for asymmetric CD8(+) T cell activation and differentiation

作者:Capece Tara; Walling Brandon L; Lim Kihong; Kim Kyun Do; Bae Seyeon; Chung Hung Li; Topham David J; Kim Minsoo*
来源:The Journal of Cell Biology, 2017, 216(11): 3817-3829.
DOI:10.1083/jcb.201609072

摘要

The integrin lymphocyte function-associated antigen 1 (LFA-1; CD11a/CD18) is a key T cell adhesion receptor that mediates stable interactions with antigen-presenting cell (APC), as well as chemokine-mediated migration. Using our newly generated CD11a-mYFP knock-in mice, we discovered that naive CD8+ T cells reserve a significant intracellular pool of LFA-1 in the uropod during migration. Intracellular LFA-1 quickly translocated to the cell surface with antigenic stimulus. Importantly, the redistribution of intracellular LFA-1 at the contact with APC was maintained during cell division and led to an unequal inheritance of LFA-1 in divided T cells. The daughter CD8+ T cells with disparate LFA-1 expression showed different patterns of migration on ICAM-1, APC interactions, and tissue retention, as well as altered effector functions. In addition, we identified Rab27 as an important regulator of the intracellular LFA-1 translocation. Collectively, our data demonstrate that an intracellular pool of LFA-1 in naive CD8+ T cells plays a key role in T cell activation and differentiation.

  • 出版日期2017-11