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Staphylococcal enterotoxin H displays unique MHC class II-binding properties.

Staphylococcal enterotoxin H (SEH) has been described as a superantigen by sequence homology with the SEA subfamily and briefly characterized for its in vivo activity. In this study, we demonstrate that SEH is a potent T cell mitogen and inducer of T cell cytotoxicity that possesses unique MHC class II-binding properties. The apparent affinity of SEH for MHC class II molecules is the highest affinity ever measured for a staphylococcal enterotoxin (Bmax1/2 approximately 0.5 nM for MHC class II expressed on Raji cells). An excess of SEA or SEAF47A, which has reduced binding to the MHC class II alpha-chain, is able to compete for binding of SEH to MHC class II, indicating an overlap in the binding sites at the MHC class II beta-chain. The binding of SEH to MHC class II is like SEA, SED, and SEE dependent on the presence of zinc ions. However, SEH, in contrast to SEA, binds to the alanine-substituted DR1 molecule, betaH81A, believed to have impaired zinc-bridging capacity. Furthermore, alanine substitution of residues D167, D203, and D208 in SEH decreases the affinity for MHC class II as well as its in vitro potency. Together, this indicates an MHC class II binding site on SEH with a different topology as compared with SEA. These unique binding properties will be beneficial for SEH to overcome MHC class II isotype variability and polymorphism as well as to allow an effective presentation on APCs also at low MHC class II surface expression.

Alanine↗

Xenografts of MHC-deficient mouse embryonic mesencephalon improve behavioral recovery in hemiparkinsonian rats.

The limited availability of human embryonic tissue for dopamine cell transplants in Parkinson's patients has led to an increased interest in using xenogeneic donor tissue. Unfortunately, without aggressive immunosuppression, such brain xenografts are rejected by the host immune system. Chronic brain xenograft rejection is largely mediated by helper T cells, which require presentation of xenoantigens by major histocompatability complex (MHC) class II for their activation. We examined survival and function of xenografts of E13 mouse mesencephalon deficient in either MHC class I, class II, or both after transplantation into adult hemiparkinsonian rats without immunosuppression. Recipients received grafts from C57BL/6 mice that were either: 1) wild-type (wt), 2) MHC class I knockout (KO), 3) MHC class II KO, 4) MHC class I and II double KO, or 5) saline sham transplants. At 6 weeks after transplantation, recipients of MHC class I KO, class II KO, and double KO xenografts significantly reduced methamphetamine-induced circling rate while rats with wt xenografts and sham-operated rats showed no improvement. MHC class II KO grafts had the greatest number of surviving dopamine neurons. All transplants, including saline sham controls, contained infiltrating host MHC class II-positive cells. Saline sham grafts and MHC class II KO xenografts contained significantly fewer infiltrating host MHC class II-positive cells than did wt grafts. Our results show that MHC class II-deficient xenografts survive transplantation for at least 6 weeks in the absence of immunosuppression, reduce rotational asymmetry, and provoke lesser immune reaction than wt grafts.

Animals↗

Specific prolongation of MHC class II disparate skin allografts by in vivo administration of anti-IFN-gamma monoclonal antibody.

In vivo rejection of MHC class II disparate skin allografts has been thought to involve IFN-gamma-induced expression of MHC class II alloantigens because less than 3% of skin epidermal cells express MHC class II alloantigens constitutively. In our study we directly tested this hypothesis by examining the effect of in vivo administered anti-IFN-gamma mAb on rejection of MHC class II disparate skin allografts, and comparing its effect on rejection of MHC class I disparate skin allografts placed on the same individual mice. We found that anti-IFN-gamma mAb blocked the rejection of MHC class II disparate skin allografts, but had no effect on the rejection of MHC class I disparate skin allografts. These results demonstrate that endogenously produced IFN-gamma is critical for rejection of MHC class II disparate skin allografts, but not for rejection of MHC class I disparate skin allografts. Thus, this study strongly supports the concept that MHC class II rejection responses require IFN-gamma induced MHC class II expression on keratinocytes of the allograft.

Animals↗

Class II MHC molecules are spontaneously internalized in acidic endosomes by activated B cells.

The antibody response to protein antigens requires specific cooperation between B and T cells. In order to deliver the helper signal, T cells must recognize, in the context of Class II MHC, processed antigen on the membrane of B cells. Processed antigen is in the form of peptides bound in a given site of the Class II MHC molecule; in order to address the question of where, in the B cell, the complex of Class II MHC and processed antigen is formed, we studied the subcellular localization of these two molecules. Since the formation of this complex is the crucial step in antigen processing and presentation, the answer to this question is central to the whole problem of the physiology of antigen handling by B cells. To collect information pertinent to the question, we have compared, in B cells, the intracellular traffic of Class II MHC and of monovalent and divalent anti-immunoglobulin antibodies used as protein ligands of the membrane immunoglobulins. We have done so by two-color immunofluorescence microscopy, and we have detected extensive confluence of Class II MHC molecules with the immunoglobulin ligand, both mono- and bi-valent, in the endosomes of LPS-activated murine B cells. Whereas the ligand clearly reaches the endosomes by internalization from the cell membrane, the Class II MHC molecules could reach the same location either by endocytosis from the membrane or through targeting to the endosomes of newly synthesized Class II MHC molecules. We have collected quantitative evidence for endocytosis of Class II MHC by following, with the fluorescence activated cell sorter, the quenching of the fluorescence of fluoresceinated Fab' anti Class II MHC in LPS-activated murine B cells; this quenching indicates the entry of the label into an acidic intracellular compartment. Together with the results of others, obtained with different methods, our observations support the concept that, at least in mature activated B cells, Class II MHC molecules reach the organelles where they meet processed protein antigens, mainly through the endocytic route. Since activated B cells endocytose their membrane Class II MHC, and not their membrane Class I, our results contribute to the understanding of how B cells present antigens, that have bound to their membrane immunoglobulins, to Class II-restricted helper T cells and not to Class I-restricted cytolytic T cells.

Animals↗

The role of the major histocompatibility complex in in vitro antibody responses; MHC restriction in responses involving linked recognition of antigenic determinants is not solely consequent to T cell-accessory cell restrictions.

Major histocompatibility complex (MHC) restrictions in the secondary antibody response in vitro to the soluble protein antigen trinitrophenyl keyhole limpet haemocyanin (TNP-KLH) were investigated. Experimental conditions were employed which ensured that co-operation between KLH-primed T cells and TNP-primed B cells was possible only through linked recognition of carrier and haptenic determinants. Under such conditions co-operation between T and B cells appears to be MHC-restricted. These experiments were designed to distinguish between two possible reasons for such MHC restrictions: (i) interaction between T and B cells is directly restricted by the MHC; or (ii) MHC-restricted T cell-antigen-presenting cell (APC) interactions limit generation of antibody responses and thus impose a pseudo-MHC restriction on T-B interactions. The ability of F1 APC to circumvent MHC restrictions was determined. The capacity of KLH-primed T cells from (P X Q)F1 leads to parent P and parent P leads to F1 X-irradiation bone marrow chimaeras to help TNP-primed parent P and parent Q B cells was assayed. Such T cells preferentially co-operate with parent P B cells. Addition of F1 APC from the spleen and the peritoneum did not alter the MHC restriction. Antibody responses stimulated by either high or low antigen concentrations were similarly MHC-restricted. Stimulation with antigen-pulsed F1 APC also failed to circumvent MHC restrictions. These results suggest that in this system involving linked recognition of antigenic determinants, the MHC directly restricts interactions between T and B cells.

Animals↗

Immunogenic peptides bind to class II MHC molecules in an early lysosomal compartment.

Exogenous protein Ag are processed within endocytic compartments to produce peptides that bind to class II MHC (MHC-II) molecules for presentation to T cells. We have now identified a subcellular compartment in which immunogenic peptides bind to MHC-II as a subset of high density lysosomes. Immunoelectron microscopy of whole cells and dense Percoll gradient subcellular fractions showed early tubulovesicular lysosomes with high levels of MHC-II. Typical mature lysosomes contained less MHC-II. Pulse-chase biosynthetic labeling of macrophages followed by immunoprecipitation of MHC-II from dense lysosomal fractions showed that MHC-II molecules targeted efficiently to lysosomes after biosynthesis. Moreover, lysosomal MHC-II molecules were rapidly loaded with immunogenic peptide (as detected by T cells) soon after exposure of macrophages to Ag and before similar expression of peptide-MHC-II complexes on the plasma membrane; this loading was blocked at 18 degrees C. We propose that nascent MHC-II molecules target to early tubulovesicular lysosomes and bind immunogenic peptides therein; the resulting peptide-MHC-II complexes are then transported to the plasma membrane.

Animals↗

Ligation of MHC class I molecules on peripheral blood T lymphocytes induces new phenotypes and functions.

Microgram concentrations of immobilized anti-MHC class I (MHC-I) Ab induced proliferation of resting CD3+ T cells from peripheral blood. In contrast, soluble Ab did not activate T cells. Exposure of T cells to immobilized anti-MHC-I Ab for only 24 h was followed by proliferation and development of T cell-mediated cytotoxicity. Immediately following MHC-I ligation, the T cells responded with increased protein tyrosine phosphorylation, with new bands appearing in the SDS-PAGE. Exposure of T cells to immobilized anti-MHC-I Ab for 24 h induced an increased surface expression of the TCR/CD3 and CD28 molecules. MHC-I-induced proliferation of purified T cells was dependent on cellular interactions with non-T cells. Under certain conditions, in which MHC-I was ligated by picogram concentrations of immobilized anti-MHC-I Ab, anti-TCR/CD3 Ab-induced proliferation of T cells was strongly inhibited. These data clearly demonstrate that ligation of the MHC-I complex on T cells may induce both positive and negative signals. Since the physiologic ligands for MHC-I molecules are TCR and the CD8 molecules, our data may suggest that MHC-I molecules are instrumental in cellular interactions between T cells.

Antibodies, Monoclonal↗

Novel immunotherapeutic strategies using MHC derived peptides.

Organ transplantation is now the treatment of choice for end stage organ failure. The ultimate goal in transplantation remains the development of strategies to induce specific tolerance to the allograft. The major histocompatibility complex (MHC) antigens are the principal targets of the immune response to allografts and T cell recognition of allo-MHC is the initial event which initiates allograft rejection. The availability of sequences of MHC genes in mice, rats and humans has made it possible to prepare synthetic peptides for the study of the role of MHC peptides in allorecognition and tolerance induction. New evidence confirms that there are at least two distinct, but not necessarily mutually exclusive, pathways of allorecognition. In the so-called "direct" pathway T cells recognize intact allo-MHC molecules on the surface of donor cells. These MHC molecules contain an array of endogenous peptides bound in their antigen presentation groove. In the "indirect" pathway, T cells recognize specific processed alloantigen presented as peptides in the context of self MHC by antigen-presenting cells (APCs). In addition, there is ample evidence that synthetic MHC peptides can immunomodulate the alloimmune response both in vitro and vivo, and that potent allo-tolerance can be induced with synthetic MHC peptides. Two types of effects mediated by synthetic MHC peptides have been demonstrated: (1) suppression of the alloimmune response by relatively non-polymorphic peptides and (2) antigen-specific unresponsiveness induced by polymorphic peptides. The mechanisms mediating the immunomodulatory effects of synthetic effects of synthetic class I and class II MHC peptides and the potential for clinical applications are reviewed.

Animals↗

In vitro and in vivo evidence for high frequency of I-Ab-reactive CD4+ T cells in HLA-DQ or HLA-DRA transgenic mice lacking endogenous MHC class I and/or class II expression.

Although T cells are educated to recognize foreign antigenic peptides in the context of self MHC molecules during their development in the thymus, peripheral T cells also recognize allo- and xeno-MHC molecules. The lower frequency of xeno-MHC-reactive T cells than that of allo-MHC-reactive T cells is often explained by the difference in the degree of homology between xeno- or allo-MHC and self MHC molecules, as well as by the species barrier of the molecules involved in immune recognition. To distinguish these two possibilities, we estimated the frequency of I-Ab-reactive CD4+ T cells selected by HLA-DQ or DR alpha E beta b molecules, using HLA-DQ6 and HLA-DRA transgenic C57BL/6 (B6) mice lacking endogenous MHC class I and/or class II molecules (DQ6A0/0 and DR alpha 30A0/0 beta 20/0). CD4+ lymph node T cells from DQ6A0/0 and DR alpha 30A0/0 beta 20/0 showed the strong proliferative response to I-Ab molecules. In addition, DQ6A0/0 and DR alpha 30A0/0 beta 20/0 rejected the skin graft from mice expressing I-Ab molecules irrespective of MHC class I expression, indicating that the CD4+ T cells recognizing I-Ab molecules are directly involved in this rejection. The estimated frequency of I-Ab-reactive CD4(+)CD8- thymocytes in DR alpha 30A0/0 beta 20/0 and DQ6A0/0 was comparable with that observed in the MHC class II-disparate strains. Our findings thus indicate that CD4+ T cells selected to mature on xeno-MHC class II molecules such as HLA-DQ6 or DR alpha E beta b, when these molecules are expressed in mice, recognize I-Ab molecules as allo-MHC class II, despite the less structural homology.

Animals↗

Diversity of Mhc class I and IIB genes in house sparrows (Passer domesticus).

In order to understand the expression and evolution of host resistance to pathogens, we need to examine the links between genetic variability at the major histocompatibility complex ( Mhc), phenotypic expression of the immune response and parasite resistance in natural populations. To do so, we characterized the Mhc class I and IIB genes of house sparrows with the goal of designing a PCR-based genotyping method for the Mhc genes using denaturing gradient gel electrophoresis (DGGE). The incredible success of house sparrows in colonizing habitats worldwide allows us to assess the importance of the variability of Mhc genes in the face of various pathogenic pressures. Isolation and sequencing of Mhc class I and IIB alleles revealed that house sparrows have fewer loci and fewer alleles than great reed warblers. In addition, the Mhc class I genes divided in two distinct lineages with different levels of polymorphism, possibly indicating different functional roles for each gene family. This organization is reminiscent of the chicken B complex and Rfp-Y system. The house sparrow Mhc hence appears to be intermediate between the great reed warbler and the chicken Mhc, both in terms of numbers of alleles and existence of within-class lineages. We specifically amplified one Mhc class I gene family and ran the PCR products on DGGE gels. The individuals screened displayed between one and ten DGGE bands, indicating that this method can be used in future studies to explore the ecological impacts of Mhc diversity.

Alleles↗

How specific MHC class I and class II combinations affect disease resistance against infectious salmon anaemia in Atlantic salmon (Salmo salar).

The aim was to evaluate the performance of selected individual MHC class I and class II alpha (A) alleles, and combinations of these on disease resistance against infectious salmon anaemia (ISA). The material consisting of 1966 fish from seven families, contained five MHC class I alleles and four MHC class II A alleles. Which representing given class II A and class II beta (B) haplotypes, totalling 19 MHC class I and class II A genotypes. The fish were challenged with infectious salmon anaemia virus (ISAV), the virus causing ISA. Dead fish were collected daily during the challenge experiment and the survivors were collected at termination. All fish were genotyped for MHC class I and class II A. The total mortality in the material was 85.14%. For MHC class I, UBA*0201 and UBA*0301 were significantly the most resistant alleles, while UBA*0601 for class I and DAA*0301 for class II A were the significantly most susceptible alleles. The analysis of combined MHC class I and class II A genotypes detected that fish with the genotype UBA*0201/*0301;DAA*0201/*0201 were the most resistant fish with a hazard ratio (HR) at 0.750, while the fish with the genotypes UBA*0601/*0801;DAA*0501/*0501 and UBA*0201/*0301;DAA*0301/*0501 were the most susceptible fish with HR of 1.334 and 1.425. In addition, Cox regression analysis within family detected combined MHC class I and class II A genotypes that contributed significantly to resistance and susceptibility. The study confirmed the expectation of performance of individual MHC class I and class II A alleles, and also detected an effect of MHC class I and class II A in combinations.

Alleles↗

Mate choice decisions of stickleback females predictably modified by MHC peptide ligands.

Sexual selection has been proposed as one mechanism to explain the maintenance of high allelic diversity in MHC genes that control the extent of resistance against pathogens and parasites in natural populations. MHC-based sexual selection is known to involve olfactory mechanisms in fish, mice, and humans. During mate choice, females of the three-spined stickleback (Gasterosteus aculeatus) use an odor-based selection strategy to achieve an optimal level of MHC diversity in their offspring, equipping them with optimal resistance toward pathogens and parasites. The molecular mechanism of odor-based mate-selection strategies is unknown. Because peptide ligands for MHC class I molecules function as individuality signals in mice, we hypothesized that female sticklebacks might assess the degree of MHC diversity of potential partners by means of the structural diversity of the corresponding peptide ligands in perceived odor signals. We show that structurally diverse MHC ligands interact with natural odors of male sticklebacks to predictably modify MHC-related mate choice. For a mating pair with suboptimal numbers of MHC alleles, peptides increase the attractiveness of male water, whereas for a mating pair with superoptimal numbers, attractiveness is decreased. Our results suggest that female sticklebacks use evolutionarily conserved structural features of MHC peptide ligands to evaluate MHC diversity of their prospective mating partners.

Amino Acid Sequence↗

Inhibitory effects of unmethylated CpG oligodeoxynucleotides on MHC class I-deficient and -proficient HPV16-associated tumours.

Unmethylated oligodeoxynucleotides containing guanine-cytidine dimers (CpG ODN) have been described as potent inducers of selected antitumour immune responses and the immunotherapeutic efficacy of CpG ODN has been examined either alone or as a vaccine adjuvant. We hypothesized that CpG ODN therapy could be an effective tool for immunotherapy of not only conventional MHC class I(+) tumours but also of those tumours that have lost MHC class I expression during their progression. To address this hypothesis, we employed the animal model resembling MHC class I-proficient and -deficient human papilloma virus (HPV) 16-associated tumours. A cell line transformed with HPV16 E6 and E7 oncogenes, TC-1, as a prototype of MHC class I-positive line, and its MHC class I-deficient sublines TC-1/A9 and TC-1/P3C10 were injected into syngeneic C57BL/6 mice and the growing tumours were subjected to immunotherapy with CpG ODN 1826. The therapy started either 1 day after the challenge with the tumour cells or later, when the tumours had reached a palpable size. In both settings, CpG ODN 1826 significantly reduced the growth of MHC class I-proficient and -deficient tumours. Furthermore, we demonstrated that CpG ODN 1585, whose mechanism of action preferably involves indirect activation of the natural killer cells, induced regression of the MHC class I-deficient tumours TC1/A9 but not of the MHC class I-proficient tumours TC-1. This study infers that synthetic CpG ODN have a potential for the therapy of both MHC class I-proficient and -deficient tumours and thus could be also used against tumours that tend to down-regulate their MHC class I expression.

Animals↗

The major histocompatibility complex in monotremes: an analysis of the evolution of Mhc class I genes across all three mammalian subclasses.

We report the isolation and characterization of cDNA clones of expressed, functional major histocompatibility complex class-I ( Mhc-I) genes from two species of monotremes: the duck-billed platypus and the short-beaked echidna. The cDNA clones were isolated from libraries constructed from spleen RNA, clearly establishing their expression in at least this one peripheral lymphoid organ. From the presence of conserved amino acid residues, it appears the expressed sequences encode molecules that likely function as classical Mhc-I. These clones were isolated using monotreme Mhc-I processed pseudogenes as probes. These processed pseudogenes were isolated from genomic DNA and, based on their structure, are likely independently derived in the platypus and echidna. When all the monotreme sequences were included in phylogenetic analyses, we found no apparent orthologous relationships between the platypus and echidna Mhc-I. Analyses that included a large number of Mhc-I sequences from other taxa support a separate monotreme Mhc-I clade, basal to a therian Mhc-I clade that is comprised of sequences from marsupial and placental mammals. The phylogenies also support the hypothesis that Mhc-I genes of placental mammals, marsupials, and monotremes are derived from three separate lineages of Mhc-I genes, best explained by two rounds of duplications and deletions. The first round would have occurred prior to the divergence of monotremes and therians, and the second prior to the divergence of marsupials and placental mammals. The sequences described here represent the first reported functional monotreme Mhc-I, as well as the first processed pseudogenes of any type from monotremes.

Amino Acid Sequence↗

Characterization of a divergent non-classical MHC class I gene in sharks.

Sharks are the most ancient group of vertebrates known to possess members of the major histocompatibility complex (MHC) gene family. For this reason, sharks provide a unique opportunity to gain insight into the evolution of the vertebrate immune system through comparative analysis. Two genes encoding proteins related to the MHC class I gene family were isolated from splenic cDNA derived from spiny dogfish shark ( Squalus acanthias). The genes have been designated MhcSqac-UAA*01 and MhcSqac-UAA*NC1. Comparative analysis demonstrates that the Sqac-UAA*01 protein sequence clusters with classical MHC class I of several shark species and has structural elements common to most classical MHC class I molecules. In contrast, Sqac-UAA*NC1 is highly divergent from all vertebrate classical MHC class I proteins, including the Sqac-UAA *01 sequence and those of other shark species. Although Sqac-UAA*NC1 is clearly related to the MHC class I gene family, no orthologous genes from other species were identified due to the high degree of sequence divergence. In fact, the Sqac NC1 protein sequence is the most divergent MHC class-I-like protein identified thus far in any shark species. This high degree of divergence is similar in magnitude to some of the MHC class-I-related genes found in mammals, such as MICA or CD1. These data support the existence of a class of highly divergent non-classical MHC class I genes in the most primitive vertebrates known to possess homologues of the MHC and other components of the adaptive immune system.

Amino Acid Sequence↗

An Mhc class I allele associated to the expression of T-dependent immune response in the house sparrow.

The major histocompatibility complex (Mhc) encodes for highly variable molecules, responsible for foreign antigen recognition and subsequent activation of immune responses in hosts. Mhc polymorphism should hence be related to pathogen resistance and immune activity, with individuals that carry either a higher diversity of Mhc alleles or one specific Mhc allele exhibiting a stronger immune response to a given antigen. Links between Mhc alleles and immune activity have never been explored in natural populations of vertebrates. To fill this gap, we challenged house sparrows (Passer domesticus) with two T-dependent antigens (phytohemagglutinin and sheep red blood cells) and examined both primary and secondary immune responses in relation to their Mhc class I genotypes. The total number of Mhc alleles had no influence on either primary or secondary response to the two antigens. One particular Mhc allele, however, was associated with an increased response to both antigens. Our results point toward a contribution of the Mhc, or of other genes in linkage disequilibrium with the Mhc, in the regulation of immune responses in a wild animal species.

Alleles↗

MHC class I genes in a New World primate, the cotton-top tamarin (Saguinus oedipus), have evolved by an active process of loci turnover.

Lymphocytes of a New World primate, the cotton-top tamarin (Saguinus oedipus), express classical G-related major histocompatibility complex (MHC) class I molecules with unusually limited polymorphism and variability. Three G-related loci, an F locus, an E locus, and two pseudogenes (So-N1 and So-N3) have been identified by cDNA library screening and extensive PCR analysis of both cDNA and genomic DNA from the cotton-top tamarin. Furthermore, each genus of the subfamily Callitrichinae (tamarins and marmosets) appears to express its own unique set of MHC class I genes, likely due to a rapid turnover of loci. The rapid emergence of unique MHC class I genes in the Callitrichinae genera, resulting from an active process of duplication and inactivation of loci, may account for the limited diversity of the MHC class I genes in the cotton-top tamarin. To determine the nature of the entire complement of MHC class I genes in the cotton-top tamarin, we synthesized a genomic DNA library and screened it with MHC class I-specific probes. We isolated nine new MHC class I pseudogenes from this library. These newly isolated tamarin G-related MHC class I pseudogenes are not closely related to any of their functional counterparts in the tamarin, suggesting that they do not share a recent common ancestral gene with the tamarin's currently expressed MHC class I loci. In addition, these tamarin sequences display a high rate of nonsynonymous substitutions in their putative peptide binding region. This indicates that the genes from which they have derived were likely subject to positive selection and, therefore, were once functional. Our data support the notion that an extremely high rate of loci turnover is largely responsible for the limited diversity of the MHC class I genes in the cotton-top tamarin.

3' Untranslated Regions↗

Characterisation of grass carp (Ctenopharyngodon idellus) MHC class I domain lineages.

In order to characterise grass carp MHC class I (Ctid-MHC I) sequences, 26 Ctid-MHC I genes were cloned from 12 individuals and their alpha domain lineages were analysed. Simultaneously, a quantitative reverse transcription-polymerase chain reaction (Q-RT-PCR) assay was developed to detect Ctid-MHC I tissue-specific expression. The results suggested that Ctid-MHC I could be divided into eight lineages (Ctid-NA-Ctid-NH). Based on whether they contained the motif of eight key amino acids (YYRTKWYY), Ctid-MHC I lineages were divided into two groups [Ctid-MHC I (8(+)) and Ctid-MHC I (8(-))]. The expression analysis showed that the Ctid-MHC I locus/loci appeared in the kidney, gill, intestine, heart, spleen, liver, and brain. A GenBank homology BLAST was performed independently with each alpha domain, and Ctid-MHC I alpha1, alpha2, and alpha3 were categorised into two (V and IX), five (II, IV-VII), and four (IV-VII) domain lineages, respectively. Based on the alphabetic labelling system created in our earlier studies, one alpha1 (IX), four alpha2 (IV-VII), and unique alpha3 (V-VII) domain lineages were observed in grass carp and across the teleostean species.

Amino Acid Sequence↗