K48- and K27-mutant ubiquitin regulates adaptive immune response by affecting cross-presentation in bone marrow precursor cells

Author:

Jia Jun Jun1,Liao Xiao Yan1,Liang Yi Yun1,Chen Rui Ling1,Gao Feng Guang1

Affiliation:

1. Department of Basic Medicine Science, School of Medicine, Xiamen University , Xiamen, Fujian, China

Abstract

Abstract K48-linked ubiquitination determines antigen degradation and plays vital roles in the process of cross-presentation of bone marrow precursor cell (BMPC)-derived dendritic cells (DCs). Although previous studies revealed that K48 and K27-linked ubiquitination regulates innate immunity, the exact roles of K48 and K27-linked ubiquitination in cross-presentation and BMPC-based adaptive immunity are still uncertain. In this study, we investigated the effects of K48- and K27-mutant ubiquitin (Ub) on BMPC-based adaptive immune response by observing the effects of MG132, Ub deficiency, and K48/K27-mutant Ub on cross-presentation, T cell proliferation, IFN-γ secretion, BMPC-based CTL priming, and thereby the efficiency of cytolytic capacity of BMPC-activate T cells. We demonstrated that MG132, Ub deficiency, and K48-mutant Ub impair cross-presentation, T cell proliferation, IFN-γ secretion, BMPC-based CTL priming, and the cytolytic capacity of BMPC-activated T cells. Moreover, although K27-only Ub decreases cross-presentation, the replenishment of K27-mutant Ub restores Ub deficiency impaireds the abilities of T cell proliferation, IFN-γ secretion, CTL priming, and the cytolytic capacity of BMPC-activated T cells. Thus, these data suggest that K48- and K27-linked ubiquitination contributes to BMPC-mediated adaptive immune response by affecting BMPC cross-presentation and the cytolytic capacity by up-regulating both perforin and granzyme B in BMPC-activated T cells. K48- and K27-mutant Ub might have potential clinical therapeutic function in adaptive immune response-associated diseases.

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Immunology,Immunology and Allergy

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