Interferon Regulatory Factors 1 and 2 Play Different Roles in MHC II Expression Mediated by CIITA in Grass Carp, Ctenopharyngodon idella.

Xiao-Bing Lu,Yong-An Zhang,Dan-Dan Chen,Long-Feng Lu,Shun Li,Pin Nie,Zhao-Xi Wang,Xiang-Yang Zhang,Shu-Bo Liu

doi:10.3389/fimmu.2019.01106

Abstract

Expression of major histocompatibility complex class II (MHC II) molecules, which determines both the immune repertoire during development and subsequent triggering of immune responses, is always under the control of a unique (MHC class II) transactivator, CIITA. The IFN-γ-inducible MHC II expression has been extensively and thoroughly studied in humans, but not in bony fish. In this study, the characterization of CIITA was identified and its functional domains were analyzed in grass carp. The absence of GAS and E-box in the promoter region of grass carp CIITA, might imply that the cooperative interaction between STAT1 and USF1 to active the CIITA expression, found in mammals, is not present in bony fish. After the transfection of IFN-γ or IFN-γ rel, only IFN-γ could induce MHC II expression mediated by CIITA. Moreover, interferon regulatory factor (IRF) 2, which cooperates with IRF1 to active the CIITA promoter IV expression in mammals, played an antagonistic role to IRF1 in the activation of grass carp CIITA. These data suggested that grass carp, compared with mammals, has both conservative and unique mechanisms in the regulation of MHC II expression.

Highlights

In vertebrates, major histocompatibility complex II (MHC II) molecules play a pivotal role in the induction of immune responses by presenting exogenous antigenic peptides to CD4+ helper T lymphocytes, resulting in their activation and differentiation [1]
The Dual-luciferase reporter experiment was carried out to detect the function of IRF2- N and IRF2- C, and the results indicated that neither IRF2- N nor IRF2- C could suppress the expression of grass carp class II transactivator (CIITA) (Figure 6E)
Many studies have shown that major histocompatibility complex class II (MHC II) molecules are indispensable in antigen presentation [28, 29]

Summary

Introduction

Major histocompatibility complex II (MHC II) molecules play a pivotal role in the induction of immune responses by presenting exogenous antigenic peptides to CD4+ helper T lymphocytes, resulting in their activation and differentiation [1]. MHC II molecules are constitutively expressed in professional antigen-presenting cells (APCs), such as B cells, dendritic cells (DCs), and macrophages [3], other non-APCs including mesenchymal stromal cells, fibroblasts, and endothelial cells, can be induced to express MHC II after stimulation with interferon (IFN)-γ [4, 5]. Both constitutive and induced MHC II expression can be further modulated by additional signals. IFN-γinduced expression of MHC II can be inhibited by numerous stimuli such as TGF-β and IL-10 [6]

Methods

Results

Conclusion