Comprehensive analysis of MHC class II genes in teleost fish genomes reveals dispensability of the peptide-loading DM system in a large part of vertebrates

Johannes M Dijkstra,Unni Grimholt,Keiichiro Hashimoto,Jong Leong,Ben F Koop

doi:10.1186/1471-2148-13-260

Johannes M Dijkstra, Unni Grimholt + Show 3 more

Open Access

https://doi.org/10.1186/1471-2148-13-260

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Abstract

BackgroundClassical major histocompatibility complex (MHC) class II molecules play an essential role in presenting peptide antigens to CD4+ T lymphocytes in the acquired immune system. The non-classical class II DM molecule, HLA-DM in the case of humans, possesses critical function in assisting the classical MHC class II molecules for proper peptide loading and is highly conserved in tetrapod species. Although the absence of DM-like genes in teleost fish has been speculated based on the results of homology searches, it has not been definitively clear whether the DM system is truly specific for tetrapods or not. To obtain a clear answer, we comprehensively searched class II genes in representative teleost fish genomes and analyzed those genes regarding the critical functional features required for the DM system.ResultsWe discovered a novel ancient class II group (DE) in teleost fish and classified teleost fish class II genes into three major groups (DA, DB and DE). Based on several criteria, we investigated the classical/non-classical nature of various class II genes and showed that only one of three groups (DA) exhibits classical-type characteristics. Analyses of predicted class II molecules revealed that the critical tryptophan residue required for a classical class II molecule in the DM system could be found only in some non-classical but not in classical-type class II molecules of teleost fish.ConclusionsTeleost fish, a major group of vertebrates, do not possess the DM system for the classical class II peptide-loading and this sophisticated system has specially evolved in the tetrapod lineage.

Highlights

Classical major histocompatibility complex (MHC) class II molecules play an essential role in presenting peptide antigens to CD4+ T lymphocytes in the acquired immune system
After digestion of the invariant chain by endosomal proteases, Class II-associated invariant chain peptide (CLIP) is dissociated from the groove by the nonclassical class II DM molecule in the MHC class II compartment (MIIC), and other peptides, including those derived from exogenous antigens, can bind to the groove of the classical MHC class II molecule [1,2,3,4,5,6]
We identified a total of 120 MHC class II genes or partial genes in the following Ensembl genomic databases: Danio rerio, Gasterosteus aculeatus, Oryzias latipes (Medaka1), Takifugu rubripes (Fugu4.0), Tetraodon nigroviridis (Tetraodon8.0) and Oreochromis niloticus (Nile tilapia; Orenil 1.0)

Summary

Introduction

Classical major histocompatibility complex (MHC) class II molecules play an essential role in presenting peptide antigens to CD4+ T lymphocytes in the acquired immune system. The highly polymorphic classical MHC class II molecules can present exogenous antigenic peptides including those derived from proteins of many pathogens to CD4+ T lymphocytes in the acquired immune system [1]. In the mammalian acquired immune system, a nonclassical MHC class II molecule, HLA-DM in humans (H2-DM in mice), plays an important role in proper peptide presentation by the classical MHC class II molecules [1,2]. After digestion of the invariant chain by endosomal proteases, CLIP is dissociated from the groove by the nonclassical class II DM molecule in the MIIC, and other peptides, including those derived from exogenous antigens, can bind to the groove of the classical MHC class II molecule [1,2,3,4,5,6]. The DM molecule itself neither exhibits classical-type polymorphism nor shows binding capacity for peptide ligands [2]

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