Primordial linkage of β2-microglobulin to the MHC

β2-Microglobulin (β2M) is believed to have arisen in a basal jawed vertebrate (gnathostome) and is the essential L chain that associates with most MHC class I molecules. It contains a distinctive molecular structure called a constant-1 Ig superfamily domain, which is shared with other adaptive immune molecules including MHC class I and class II. Despite its structural similarity to class I and class II and its conserved function, β2M is encoded outside the MHC in all examined species from bony fish to mammals, but it is assumed to have translocated from its original location within the MHC early in gnathostome evolution. We screened a nurse shark bacterial artificial chromosome library and isolated clones containing β2M genes. A gene present in the MHC of all other vertebrates (ring3) was found in the bacterial artificial chromosome clone, and the close linkage of ring3 and β2M to MHC class I and class II genes was determined by single-strand conformational polymorphism and allele-specific PCR. This study satisfies the long-held conjecture that β2M was linked to the primordial MHC (Ur MHC); furthermore, the apparent stability of the shark genome may yield other genes predicted to have had a primordial association with the MHC specifically and with immunity in general.     

Class II MHC: sweetening the peptide only diet?

MHC molecules typically bind peptides to create ligands for the T cell antigen receptor. In this issue of Cell, report an unexpected association of class II MHC molecules with processed zwitterionic polysaccharides from pathogenic bacteria. The complexes appear to modulate the T cell dependent pathology of abscess formation.     

Does the polymorphism of MHC class II promoters matter?

The promoters of genes of the major histocompatibility complex vary not only because of linkage disequilibrium with their coding sequences but also, we argue, because of natural selection that acts particularly strongly on MHC II gene promoters. Thus, the promoter of H2Eb varies more than that of H2K, to an extent that cannot be accounted for by coding variation, and the same applies to HLA.DRB1 in comparison with H2D. We discuss how transduction by lentivirus vectors followed by adoptive transfer of monoclonal T cells could be used to test the functional activity of variant mouse promoters in vivo, and how homologous recombination in suitable cell lines might provide a short cut to obtaining promoter knock-ins.     

MHC基因复合体

主要组织相容性基因复合体(Major Histocompatibility Complex)是指位于染色体上的,控制同种异基因抗原的组织排斥和控制某些免疫反应的一组基因群。由它们控制的细胞表面抗原分别称为组织相容性抗原(Histocompatibility)和免疫反应相关抗原(Iregion associated antigen 简称 Ia 抗原)。人的 MHC 位于第6条染色体的短臂上,由四个紧密连锁的不同位点(HLA—A,B,C,D)构成,已知由它控制的组织相容性抗原有77个。小鼠的 MHC 位于第17对染色体上,包括五个区(K,I,S,G,D),已知由它控制的组织相容性抗原有56个,Ia 抗原有22个。目前已知 MHC 中包含三大类基因群,第一类基因群控制病毒感染细胞和化学改变细胞的表面抗原和控制组     

Characterization of the MHC class II ��-chain gene in ducks

In humans, classical MHC class II molecules include DQ, DR, and DP, which are similar in structure but consist of distinct α- and β-chains. The genes encoding these molecules are all located in the MHC class II gene region. In non-mammalian vertebrates such as chickens, only a single class II α-chain gene corresponding to the human DRA has been identified. Here, we report a characterization of the duck MHC class II α-chain (Anpl-DRA) encoding gene, which contains four exons encoding a typical signal peptide, a peptide-binding α1 domain, an immunoglobulin-like α2 domain, and Tm/Cyt, respectively. This gene is present in the duck genome as a single copy and is highly expressed in the spleen. Sequencing of cDNA and genomic DNA of the Anpl-DRA of different duck individuals/strains revealed low levels of genetic polymorphism, especially in the same strain, although most duck individuals have two different alleles. Otherwise, we found that the duck gene is located next to class II β genes, which is the same as in humans but different from the situation in chickens.     

Why does the immune system of Atlantic cod lack MHC II?

MHC II, a major feature of the adaptive immune system, is lacking in Atlantic cod, and there are different scenarios (metabolic cost hypothesis or functional shift hypothesis) that might explain this loss. The lack of MHC II coincides with an increased number of genes for MHC I and Toll-like receptors (TLRs).     

Physical mapping and evolution of the centromeric class I gene-containing region of the rat MHC

We physically mapped the centromeric part of the BN rat MHC (RT1n haplotype) in a contig of overlapping P1-derived artificial chromosome (PAC) clones encompassing about 300 kb. The following genes were identified and ordered as: (Syngap, Hset, Daxx, Bing1)-Tapbp-Rgl2-Ke2-Bing4-B3galt4- Rps18-Sacm2l-RT1-A1-RT1-A2-RT1-A3-Ring1-Ring2-++ +Ke4-Rxrb-Col11a2-RT1-Hb-Ring3-RT1-DMb. Thus, in contrast to other RT1 haplotypes, RT1n contains three class I genes, RT1-A1, RT1-A2, and RT1-A3, mapping between the Sacm2l and Ring1 genes. Comparisons of the sequences flanking the Sacm2L and Ring1 genes in rat, human, and mouse suggest that the class I gene-containing region was inserted between these genes in rat and mouse at a similar position. Thus, this insertion is likely to have occurred in a common ancestor of these rodents, although the presence of a site particularly permissive for insertions cannot be excluded.     

Characterization of the MHC class I region of the Japanese pufferfish (Fugu rubripes)

A BAC map of the Japanese pufferfish (Fugu) MHC class I region was constructed using a mixture of sequence scanning and sequence-tagged site mapping methodologies. The Fugu MHC class Ia genes are linked to genes which are found within the human classical MHC class II and extended class II regions, a situation which has been found in the MHC of all teleosts mapped so far. The 300-kb contig comprises 24 MHC-related genes and is bounded by six non-MHC genes, which are thought to represent an evolutionary breakpoint within the region. Comparative analysis with both human and zebrafish MHC maps indicates two blocks of genes (KNSL2, ZNF297, DAXX, TAPBP, FLOTILLIN; and PSMB8, PSMB10, PSMB9, ABCB3, FABGL, BRD2, COL11A2, RXRB) which have remained linked over 400 million years and may represent an ancestral arrangement of the vertebrate MHC. Zebrafish and Fugu diverged between 100-200 million years ago and differences exist between these two fish species. The position and number of MHC class Ia genes is not conserved between species, there is an inversion of a block of nine genes centering on the PSMB cluster, and additional genes are present in zebrafish coding for a transport-associated protein and a beta proteasome subunit. The extent of these differences has implications for the extrapolation of fish model organism data to commercial aquaculture species. The data presented here represent the most extensive analysis of a fish MHC class Ia region described so far and clearly delimit the extent of this region in Fugu and, potentially, all teleosts.     

家禽MHC结构研究进展

禽主要组织相容性复合体(Major histocompatibility complex,MHC)的结构与禽病防控、禽免疫学、禽类遗传学研究密切相关。文章对鸡、火鸡、鹌鹑、鸭和鹅的MHC结构方面的研究进展进行了综述,表明其有以下共同特点:都有保守的MHC区域,包括MHC I基因和MHC II基因及一些功能未知基因;基因排列简单而紧凑;MHC I基因内含子的长度都比哺乳动物小;鸡、火鸡、鸭和鹅的MHC I基因组序列都有8个外显子和7个内含子,MHC IIβ基因组序列都有6个外显子和5个内含子;鸡、火鸡和鹌鹑的BG基因结构模式相同;都存在微卫星重复单元。但也存在种属差异:鸡的MHC I基因和MHC II基因是双拷贝,而鸭、鹅和鹌鹑有若干个拷贝;BG基因的拷贝数及其外显子数目不同。对主要家禽MHC结构进行分析比较,将有利于对禽病学及禽免疫遗传学的进究。     

两栖动物MHC基因研究进展

MHC是高度多态的基因群,广泛分布于各种脊椎动物体内。由于MHC基因的多态性,使其在脊椎动物的免疫、遗传、进化、保护等许多方面的研究倍受关注。本文综述了两栖类MHC基因自研究以来国内外有关该基因的研究报道,包括其结构、功能以及在两栖类遗传进化、种群遗传学、免疫遗传学及抗病中的应用,并对研究前景进行了展望。     

爬行动物MHC基因研究进展

主要组织相容性复合体(MHC)是有颌脊椎动物中发现的编码免疫球蛋白受体的高度多态的基因群,因其在免疫系统中的重要作用而备受关注。脊椎动物不同支系间MHC的结构和演化差异较大。尽管MHC基因特征在哺乳类、鸟类、两栖类和鱼类中已被较好地描述,但对爬行动物MHC的了解仍较少。鉴于爬行动物对于理解MHC基因的演化占据很重要的系统发育位置,研究其MHC具有重要意义。本文就近年来爬行动物MHC的分子结构、多态性维持机制、功能和主要应用的研究现状进行了系统地回顾和总结,并展望了其研究前景。     

Are large wattles related to particular MHC genotypes in the male pheasant?

In sexually dimorphic species, partners can assess heritable mate quality by analyzing costly sexual ornaments in terms of their dimension and possibly of their symmetry. In vertebrates an important aspect of genetic quality is the efficiency of the immune system, and in particular the Major Histocompatibility Complex (MHC). If ornaments are honest advertisements of pathogen resistance (good genes), in line with the Hamilton-Zuk hypothesis, a correlation between ornament expression and MHC profiles should exist. We tested this hypothesis in the common pheasant Phasianus colchicus by comparing male ornament characteristics (wattle and spur size, and wattle fluctuating asymmetry) with a portion of exon 2 of the class IIB MHC genes containing 19 putative antigen recognition sites. A total of 8 new alleles was observed in the MHCPhco exon IIB. We found significant differences in the occurrence of MHC genotypes between males carrying large or small wattles. Homozygous genotypes predicted large wattle males more correctly than small wattle males. The association between the dimension of the spur and the occurrence of MHC genotypes was marginally significant, however, we did not find any significant association between MHC genotypes and asymmetry. Our results suggest that female pheasants may use the ornament size as a cue to evaluate male quality and thus choose males carrying particular MHC profiles.     

Molecular evidence for five distinct MHC class II α genes in the rabbit

Human HLA class 11 gene probes were used to identify five distinct genes encoding the class 11 heavy chain (a chain) in the rabbit. The rabbit genes were defined by both mapping data and hybridization studies of genomic clones derived from the inbred B/J rabbit strain. Analysis of the clones by hybridization at graded stringencies indicated that one group of clones corresponded to HLA-DR, one group to HLA-DQ, and two groups to HLA-DP. Clones within a fifth group, designated DN, hybridized weakly to HLA-DR and may carry a fourth species of class II genes in the rabbit. Clones within the group showing high homology to HLA-DR were found to also contain sequences hybridizing with a probe for HLA-DR . No HLA-DP, -DQ, or -DR sequences were detected in any of the other class II clones. Distinct banding patterns observed in Southern blot analyses using either human or rabbit class II probes revealed restriction fragment length polymorphism for the different rabbit haplotypes studied. TheDN, DQ, andDR genes appear to be present as single copies whereas there are two distinctDP-like genes in the rabbit.Abbreviations used in this paper RLA major histocompatibility complex of the rabbit - RFLP restriction fragment length polymorphism - RL-5 rabbit T-cell line - SSC 0.15 M sodium chloride, 0.015 M sodium citrate     

Characterization of the MHC class I-related MR1 locus in nonhuman primates

We characterized the MHC-related 1 ( MR1) locus in two nonhuman primates species, Pongo pygmaeus and Pan troglodytes. MR1 cDNA sequences encoding several isoforms generated through alternative splicing were observed in both species. Amino acid alignment between the five species in which MR1 has been characterized to date - human, chimpanzee, orangutan, mouse, and rat - reveals a very high degree of conservation specially in the alpha1 and alpha2 domains of the molecule. The main differences concentrate in the transmembrane and cytoplasmic domains. In the three primates species there is a lysine residue inside the putative transmembrane domain which is not present in rodents. Furthermore, the MR1 cytoplasmic region is longer in rodents, with a conserved serine-containing motif that could be involved in endocytosis; remarkably, this motif is absent in the three primate species. We also describe the presence in the chimpanzee of a sequence homologous to the MR1P1 pseudogene previously found in humans.     

Comparative and evolutionary analysis of the rhesus macaque extended MHC class II region

The sequence-based map of a part of the rhesus macaque major histocompatibility complex (MHC) extended class II region is presented. The sequenced region encompasses 67,401 bp and contains the SACM2L, RING1, FABGL and KE4 genes, as well as the HTATSF1-like and ZNF-like pseudogenes. Similar to human, but different from rat and mouse, no class I genes are found in the SACM2L- RING1 interval. The rhesus macaque extended MHC class II region shows a high degree of conservation of exonic as well as intronic and intergenic sequences compared with the respective human region. It is concluded that this particular genomic organization of the extended class II region-i.e., the absence of class I genes and the presence of the HTATSF1-like and ZNF-like pseudogenes-can be traced back to a common ancestor of humans and rhesus macaques about 23 million years ago.