Major histocompatibility complex genes and evidence for their occurrence in the tilapia, Oreochromis niloticus
Major histocompatibility complex in fish
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| 3.1.3 Major histocompatibility complex in fish
The major histocompatibility complex (MHC) is a cluster of closely linked genes present in all vertebrate species. The genes of the MHC are inherited as a unit, a phenomenon known as linkage, i.e. they make a linkage between antigenic peptides and T lymphocytes. In fact, MHC genes encode essentially polymorphic cell surface glycoproteins which bind non-self peptides (degraded antigen) and present them to T lymphocytes (Townsend and Bodmer, 1989; Bjorkman and Parham, 1990) and thus initiate a specific immune response (Klein, 1986; Rothbard and Gefter, 1991). To date, most of the work on MHC has been undertaken in homeothermic mammals and birds, and there is much less known about the system in lower vertebrates and invertebrates. Although phylogenetically, fishes are lower vertebrates, they possess the ability to mount a humoral immune response characterized by the induction of antigen specific immunoglobulins (Smith et al., 1966; Dorson, 1981). Cellular alloreactivity can be observed through allograft rejection and mixed lymphocyte reactivity (Etlinger et al., 1977; Rijkers, 1982). Teleost fish also appear to process functional lymphocyte subpopulations comparable to the T and B lymphocytes seen in higher vertebrate species (Secombes et al., 1983; Miller et al., 1986). These indirect features of the immune system indicate the presence of a putative MHC homologue in fish but the evidence still remains conjectural. In amphibians, for analysis of MHC, skin grafting between unrelated and related species has commonly been used. Cohen (1971) observed that urodelous amphibians typically rejected allografts slowly, which indicated the lack of an MHC complex, whereas anurous frog of the genus Rana characteristically exhibited acute allograft responses when appropriately challenged (Bovbjerg, 1966). The acute nature of allograft reactions among outbred frogs is seen as evidence for the existence of a major histocompatibility complex. Similar studies in teleosts also showed allografts to be rejected in an acute fashion (Borysenko, 1976; Botham et al., 1980) and that a number of histocompatibility loci (4-7) were likely to be involved in this process in goldfish (Hildemann and Owen, 1956) and between 10-15 loci in different Xiphophorus species (Kallman, 1964). Therefore, allograft rejection experiments in fish have served a dual purpose. Several scientists have used allograft experiments as a tool to investigate the developmental status of cellular immunity (Rijkers and Van Muiswinkel, 1977; Botham and Manning, 1981; Kikuchi and Egami, 1983), while others were more concerned with the genetics of tissue transplantation because there is a difference in the kinetics of graft rejection (reviewed in Hildemann, 1970; Kallman, 1970). Vertebrate animals are diploid and in nature mostly heterozygous at their MHC loci (Klein, 1986). The kinetics of graft rejection depends on the degree of heterozygosity at MHC loci in a given animal. In humans, the MHC complex is designated HLA which is located at four loci- HLA-A, HLA-B, HLA-C, and HLA-D and each of the four loci has a series of alleles. At present the HLA-B gene appears to be the most polymorphic with at least 32 distinct alleles and is followed by the HLA-A gene with at least 17 alleles. The other two genes, HLA-C and HLA-D have 8 and 12 alleles respectively. In mouse, the MHC complex is known as H-2 which has 4 loci, K, I, S, and D. At K locus more than 55 and at D locus 60 alleles have been identified (Zaleski et al., 1983). Therefore in studies on the genetics of MHC, it is seen as very important to reduce the heterozygosity at MHC loci. In many species this can be done by producing inbred lines using gynogenesis or androgenesis or at least congenic lines. Du Pasquier et al. (1977) used gynogenesis in Xenopus laevis to provide evidence of the XLA complex, the MHC homologue in this species. Komen et al. (1990) observed that skin allografts exchanged among heterozygous gynogenetic siblings produced by meiotic gynogenesis survived for a longer period, whereas allografts exchanged among homozygous gynogenetic siblings produced by mitotic gynogenesis all rejected after a shorter period. Allografts on the clonal members derived from a homozygous female were fully accepted. Likewise, the related F1 hybrids produced from the homozygous female by crossing with a homozygous male sibling accepted the grafts from the homozygous strain member, but the reverse grafts were rejected. Therefore, these results provide evidence for the idea that in carp histocompatibility genes exist, and that there is at least one major locus, and/or co-dominantly expressed multiple minor loci. In mice, rats, and humans, the major histocompatibility locus produces strong transplantation antigens which exert intense allograft reactions (Amos et al., 1963; Elkins and Palm, 1966). But other minor histocompatibility loci from other chromosomes produce weak transplantation antigens that individually trigger relatively mild immune responses (Graff and Bailey, 1973, Hildemann, 1971). Mixed lymphocyte reaction (MLR) experiments have been used to provide evidence for MHC genes in animals. In higher vertebrates, it is established that only MHC loci encoding class II molecules are responsible for MLR. The MLR have also been observed in a number of fish species such as Atlantic salmon, Salmo salar (Smith and Braun-Nesje, 1982), rainbow trout, O. mykiss (Etlinger et al., 1977), carp, C. carpio (Caspi and Avtalion, 1984; Grondel and Harmsen, 1984), and channel catfish, Ictalurus punctatus (Miller et al., 1986). Among them, Caspi and Avtalion (1984) first described the usefulness of the technique for genetic analysis of MLR-recognised histocompatibility antigens in carp. In this study, the MLR responses between fish collected from different geographical locations were invariably medium to high, whereas fishes from a single source showed uniformly low responses which might be the consequence of some degree of inbreeding. In recent years, molecular cloning techniques have facilitated the analysis of MHC in mammals. According to Klein (1986), MHC class II A and class II B genes have been cloned from a number of mammalian species. The mammalian class II molecules consist of one α and β chain and these two chains are encoded by separate class II A and class II B genes respectively. In the case of non-mammalian species, the MHC of the chicken (Gallus gallus) in which sequencing has identified classical class I (B-F), class II (B-L), and non-classical (B-G) genes (Bourlet et al., 1988; Guillemot et al., 1988). The genetic organisation of the MHC of chicken shows striking differences compared to that of mammals especially the distance between class I and class II molecules which are much shorter and interspersed with non-classical MHC genes (reviewed in Stet and Egberts, 1991). To identify and isolate the MHC genes in an animal, cross hybridisation with homologous DNA probes already isolated from higher vertebrates can be used. In this way, the human MHC class II subprobe (HLA-DQ) was successfully used to isolate the class II gene from chicken (Bourlet et al., 1988) but in fish such attempts have generally been unsuccessful (reviewed by Kaufman et. al., 1990; Stet and Egberts, 1991). Recently, the introduction of the polymerase chain reaction (PCR) and nucleotide sequence techniques have accelerated the cloning of MHC genes from lower vertebrates which has led to both cDNA and genomic sequences from a variety of teleost fishes being obtained (Hashimoto et al., 1990; Juul-Madsen et al., 1992; Hordvik et al., 1993; Ono et al., 1992, 1993; Klein et al., 1993) and cartilagenous fishes (Hashimoto et al., 1992; Kasahara et al., 1992). Hashimoto et al. (1990) first identified two putative MHC-antigen encoding sequences, TLAI-1 and TLAII-1 in carp, C. carpio which were homologous to both mammalian and avian MHC class I heavy chain and class II chain respectively. The primers used for amplification of these sequences were synthesised from two highly conserved amino acid sequence blocks surrounding two cysteine residues in the second domain of MHC class II chains as well as the third domain of class I heavy chains of human, mouse and chicken. Cloning of the 2 -microglobulin gene has been used as an alternative possible means for identifying the teleostean MHC molecules because of its non-covalent association with class I molecules (Shalev et al., 1981; Ono et al., 1993). Recently it has been known that the organisatiion of fish MHC genes is quite different from mammalian MHC (Stet et al., 1998). The similarity in amino acid sequences between fish and mammalian MHC molecules is relatively low, the maximum homology that has been found is only 40%. Sequence data of MHC genes in fish has provided information on the level of polymorphism in a single locus. Klein et al. (1993) found extensive MHC variability in cichlid fishes of lake Malawi. They found high sequence variability of the MHC class II B genes in a sample and suggested that this variability can be used as a set of molecular markers for studying speciation during adaptive radiation. High levels of polymorphism in the MHC class II genes in teleosts have been reported by Stet et al. (1996) and Langefors et al. (1997). Polymorphism of MHC genes can be used for stock identification and in the management of its improvement. Van der Zijpp and Egbert (1989) reported an association between MHC and disease in farm animals. If MHC polymorphism can be associated with disease resistance or susceptibility this information can be included in a selective breeding programme. In fact, it has been reported that several strains of fish differ in resistance or susceptibility (reviewed by Chevassus and Dorson, 1990). In the present study, two different approaches were taken to determine the levels of MHC variation and effect in different clonal groups of tilapia, O. niloticus. Firstly, polymerase chain reaction (PCR) and secondly, scale grafting. Proteasome Virus infected cell Peptides Class I MHC Rough endoplasmic reticulum Peptide Peptide presentation on Class I MHC to CD8 TC cell Bacteria Peptides Endocytic compartments Class II MHC Golgi complex Invariant chain Peptide presentation on Class II MHC molecules to CD4 TH cell TH cell Lymphokines B lymphocyte Activated B lymphocyte Antibody Endogenous pathway (Class I MHC) Exogenous pathway (Class II MHC) Figure 3.1 Schematic diagram of the antigen presenting cells involved in cellular immune system (Cited from Kuby, 1997) Nucleus CD8 Killing of altered self-cell Altered self-cell Lysis CD4 Cytotoxic T lymphocyte Download 1.2 Mb. Share with your friends:
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