首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 31 毫秒
1.
Major histocompatibility complex (MHC) class I genes encode highly polymorphic molecules that are expressed on virtually every cell type, and have been identified in all but the most primitive vertebrates. They play a number of crucial roles in the immune response to infectious disease. Most information regarding MHC genes has been generated from humans and mice but, because of the great variability found in the MHC system, it is not always possible to extrapolate from these to other species. Many strategies have evolved to maximise the ability of the MHC to protect individuals and populations against pathogens. Cattle MHC class I genes exhibit a number of unusual features. Evidence from mapping studies, haplotype and phylogenetic analyses suggests the presence of six classical class I loci, in contrast to the more usual two or three, and these are expressed in various combinations of one, two or three on different haplotypes. Although it remains difficult to assign alleles to loci, it appears that none of the loci are expressed on all haplotypes. There is currently limited information relating to polymorphism, but various approaches suggest diversity is high, and may vary between breeds/populations. Functional consequences of variable MHC haplotype composition are discussed. Identifying unique features of the MHC in cattle will lead to new insights into evolution of the immune system.  相似文献   

2.
Disease is a major source of economic loss to the livestock industry. Understanding the role of genetic factors in immune responsiveness and disease resistance should provide new approaches to the control of disease through development of safe synthetic subunit vaccines and breeding for disease resistance. The major histocompatibility complex (MHC) has been an important candidate locus for immune responsiveness studies. However, it is clear that other loci play an important role. Identifying these and quantifying the relative importance of MHC and non-MHC genes should result in new insights into host-pathogen interactions, and information that can be exploited by vaccine designers. The rapidly increasing information available about the bovine genome and the identification of polymorphisms in immune-related genes will offer potential candidates that control immune responses to vaccines. The bovine MHC, BoLA, encodes two distinct isotypes of class II molecules, DR and DQ, and in about half the common haplotypes the DQ genes are duplicated and expressed. DQ molecules are composed of two polymorphic chains whereas DR consists of one polymorphic and one non-polymorphic chain. Although, it is clear that MHC polymorphism is related to immune responsiveness, it is less clear how different allelic and locus products influence the outcome of an immune response in terms of generating protective immunity in outbred animals. A peptide derived from foot-and-mouth disease virus (FMDV) was used as a probe for BoLA class II function. Both DR and DQ are involved in antigen presentation. In an analysis of T-cell clones specific for the peptide, distinct biases to particular restriction elements were observed. In addition inter-haplotype pairings of DQA and DQB molecules produced functional molecules, which greatly increases the numbers of possible restriction elements, compared with the number of genes, particularly in cattle with duplicated DQ genes. In a vaccine trial with several peptides derived from FMDV, BoLA class II DRB3 polymorphisms were correlated with both protection and non-protection. Although variation in immune responsiveness to the FMDV peptide between different individuals is partly explainable by BoLA class II alleles, other genetic factors play an important role. In a quantitative trait locus project, employing a second-generation cross between Charolais and Holstein cattle, significant sire and breed effects were also observed in T-cell, cytokine and antibody responses to the FMDV peptide. These results suggest that both MHC and non-MHC genes play a role in regulating bovine immune traits of relevance to vaccine design. Identifying these genes and quantifying their relative contributions is the subject of further studies.  相似文献   

3.
The MHC of cattle, known as the bovine leukocyte antigen (BoLA) complex, plays an integral role in disease and parasite susceptibility, and immune responsiveness of the host. While susceptibility to tick infestation in cattle is believed to be heritable, genes that may be responsible for the manifestation of this phenotype remain elusive. In an effort to analyze the role that genes within the BoLA complex may play in host resistance to ticks, we have evaluated components of this system within a herd of cattle established at our laboratory that has been phenotyped for ectoparasite susceptibility. Of three microsatellite loci within the BoLA complex analyzed, alleles of two microsatellite loci within the BoLA class IIa cluster (DRB1-118 and DRB3-174) associated with the tick-resistant phenotype, prompting further investigation of gene sequences within the DRB3 region. DRB3 is a class IIa gene, the second exon of which is highly polymorphic since it encodes the antigen recognition site of the DR class II molecule. Analysis of the second exon of the DRB3 gene from the phenotyped calves in our herd revealed a significant association between the DRB3*4401 allele and the tick-resistant phenotype. To our knowledge, this is the first report of a putative association between a class IIa DRB3 sequence and host resistance to the Lone Star tick. Elucidation of the mechanism involved in tick resistance will contribute to improving breeding schemes for parasite resistance, which will be beneficial to the cattle industry.  相似文献   

4.
Major histocompatibility complex (MHC) class I restricted cellular immune responses play an important role in immunity to intracellular pathogens. By binding antigenic peptides and presenting them to T cells, class I molecules impose significant selection on the targets of immune responses. Candidate vaccine antigens for cellular immune responses should therefore be analysed in the context of MHC class I antigen presentation. Transgenic mice expressing human MHC (HLA) genes provide a useful model for the identification of potential cytotoxic T lymphocyte (CTL) antigens. To facilitate the analysis of candidate CTL vaccines in cattle, we have produced transgenic mice expressing a common bovine MHC (BoLA) class I allele.The functional BoLA-A11 gene, carried on a 7 kb genomic DNA fragment, was used to make transgenic mice by pronuclear microinjection. Three transgenic mouse lines carrying the BoLA-A11 gene were established. Expression of the BoLA-A11 gene was found in RNA and the A11 product could be detected on the surface of spleen and blood cells. Functional analysis of the A11 transgene product, and its ability to act as an antigen presenting molecules in the mouse host will be discussed.  相似文献   

5.
The major histocompatibility complex (MHC) of cattle is known as the bovine leukocyte antigen (BoLA) and is located on chromosome 23. BoLA has been linked to variation in resistance to disease including bovine leukemia virus‐induced lymphoma and mastitis. Moreover, BoLA appears to influence other traits such as milk yield, growth and reproduction, which are not often measured in humans, and variations in individual immune response to antigen. The BoLA appears to be organized in a similar way to the MHC region in humans, but there are notable differences. A major rearrangement within the class II region has led to the division of the BoLA into two distinct subregions of chromosome 23 separated by about a third of the chromosome’s length. The class IIa subregion contains functionally expressed DR and DQ genes, while the class IIb subregion contains the genes of undefined status such as DYA, DYB, DMA, DMB, DOB, DOA, TAP1, TAP2, LAP2 and LMP7. In addition, one pair of human class II genes (DP) does not appear to have an equivalent in cattle, and there is one pair of DY genes that seem to be found only cattle, sheep and goats. In humans, three classical, polymorphic class I genes (HLA‐A, ‐B and ‐C ) are each present on all haplotypes. However, in cattle, none of the four (or more) classical class‐I genes identified are consistently expressed, and haplotypes differ from one to another in both the gene number and composition. These variations in both class I and II are likely to play an important role in cattle immune responses. This review summarizes current knowledge of the structural and functional features and disease association of BoLA genes.  相似文献   

6.
Threatened species typically have a small or declining population size, which make them highly susceptible to loss of genetic diversity through genetic drift and inbreeding. Genetic diversity determines the evolutionary potential of a species; therefore, maintaining the genetic diversity of threatened species is essential for their conservation. In this study, we assessed the genetic diversity of the adaptive major histocompatibility complex (MHC) genes in an endangered and narrowly distributed amphibian species, Leptobrachium leishanense in Southwest China. We compared the genetic variation of MHC class I genes with that observed in neutral markers (5 microsatellite loci and cytochrome b gene) to elucidate the relative roles of genetic drift and natural selection in shaping the current MHC polymorphism in this species. We found a high level of genetic diversity in this population at both MHC and neutral markers compared with other threatened amphibian species. Historical positive selection was evident in the MHC class I genes. The higher allelic richness in MHC markers compared with that of microsatellite loci suggests that selection rather than genetic drift plays a prominent role in shaping the MHC variation pattern, as drift can affect all the genome in a similar way but selection directly targets MHC genes. Although demographic analysis revealed no recent bottleneck events in L. leishanense, additional population decline will accelerate the dangerous status for this species. We suggest that the conservation management of L. leishanense should concentrate on maximizing the retention of genetic diversity through preventing their continuous population decline. Protecting their living habitats and forbidding illegal hunting are the most important measures for conservation of L. leishanense.  相似文献   

7.
Trypanosomosis caused by infection with protozoan parasites of the genus Trypanosoma is a major health constraint to cattle production in many African countries. One hundred and seventy one Bos indicus cattle from traditional pastoral Maasai (87) and more intensively managed Boran (84) animals in Tanzania were screened by PCR for the presence of African animal trypanosomes (Trypanosoma congolense, Trypanosoma vivax and Trypanosoma brucei), using blood samples archived on FTA cards. All cattle screened for trypanosomes were also genotyped at the highly polymorphic major histocompatibility complex (MHC) class II DRB3 locus to investigate possible associations between host MHC and trypanosome infection. Overall, 23.4% of the 171 cattle tested positive for at least one of the three trypanosome species. The prevalence of individual trypanosome species was 8.8% (T. congolense), 4.7% (T. vivax) and 15.8% (T. brucei). The high prevalence of T. brucei compared with T. congolense and T. vivax was unexpected as this species has previously been considered to be of lesser importance in terms of African bovine trypanosomosis. Significantly higher numbers of Maasai cattle were infected with T. brucei (23.0%, p=0.009) and T. congolense (13.8%, p=0.019) compared with Boran cattle (8.3% and 3.6%, respectively). Analysis of BoLA-DRB3 diversity in this cohort identified extensive allelic diversity. Thirty-three BoLA-DRB3 PCR-RFLP defined alleles were identified. One allele (DRB3*15) was significantly associated with an increased risk (odds ratio, OR=2.71, p=0.034) of T. brucei infection and three alleles (DRB3*35, *16 and *23) were associated with increased risk of T. congolense infection. While further work is required to dissect the role of these alleles in susceptibility to T. brucei and T. congolense infections, this study demonstrates the utility of FTA archived blood samples in combined molecular analyses of both host and pathogen.  相似文献   

8.
To identify and characterize the bovine major histocompatibility complex (MHC) class I molecules, a panel of 11 monoclonal antibodies (mAbs) were analyzed. The mAbs reacted with bovine MHC class I antigens, as assessed by flow cytometry and immunoprecipitation followed by one- and two-dimensional gel electrophoresis. Analysis by flow cytometry revealed that class I molecules were expressed less on a class I mutant B-lymphoblastoid cell line than on the parent cell line. The relative molecular weights of the proteins identified by these mAbs were similar to those reported previously for cattle and humans. Nonequilibrium pH gradient two-dimensional gel electrophoresis showed that RH16C recognized four different class I gene products, indicating this mAb reacts with a conserved epitope present on different class I molecules. These mAbs effectively blocked cytotoxic T lymphocyte killing of allogeneic lymphoblasts, suggesting the functional importance of beta-2m in this process. These mAbs should be useful reagents for studying bovine MHC class I molecules.  相似文献   

9.
Cattle play a very important role in agriculture and food security in Vietnam. A high level of cattle diversity exists and serves different needs of Vietnamese cattle keepers but has not yet been molecularly characterized. This study evaluates the genetic diversity and structure of Vietnamese indigenous cattle populations, using microsatellite markers. A total of 410 individuals from six indigenous cattle populations and an exotic breed was characterized using 27 microsatellite markers A total of 362 alleles was detected and the number of alleles per locus ranged from 8 (INRA005 and ILSTS005) to 17 (ETH185). The level of gene diversity was high indicated by a mean expected heterozygosity (He) across populations and loci of 0.73. Level of inbreeding (mean FIS=0.05) and genetic differentiation (mean FST=0.04) was moderate. The phylogenetic tree based on Reynolds genetic distance reflected geographic distances. Structure analysis indicated five homogeneous clusters. The Brahman, Lang Son, Ha Giang and U Dau Riu cattle were assigned to independent clusters while Nghe An, Thanh Hoa and Phu Yen cattle were grouped in a single cluster. We conclude that Vietnamese indigenous cattle have high levels of genetic diversity and distinct genetic structures. Based on these results, we recommend that for conservation homogenous populations (Nghe An, Thanh Hoa and Phu Yen) can be grouped to reduce costs and U Dau Riu, Lang Son and Ha Giang populations should be conserved separately to avoid loss of genetic diversity.  相似文献   

10.
The major histocompatibility complex (MHC) is a gene complex closely linked to the vertebrate immune system due to its importance in antigen recognition and immune response to pathogens. To improve our understanding of the MHC and disease resistance in dairy cattle, we gathered 5119 test day records of somatic cell count (SCC) and performance traits of 262 Holstein dairy cows to determine whether the DRB region of the MHC contains alleles that are associated with elevated SCC, milk yield, protein and fat percent of milk. To this purpose, genotyping of animals for DRB3 gene was investigated by polymerase chain reaction‐based restriction fragment length polymorphism (PCR‐RFLP) assay. A two‐step PCR was carried out so as to amplify a 284 base‐pair fragment of exon 2 of the target gene. Second PCR products were treated with three restriction endonuclease enzymes RsaI, BstYI and HaeIII. Twenty‐eight BoLA‐DRB3 alleles were identified including one novel allele (*40). The results in general are in good accordance with allele frequencies of Holstein cattle populations reported by previous studies. Analyses of associations were modeled based on repeated measurement anova and generalized logistic linear methods for production traits and SCC data, respectively. The results of this study showed a significant relationship between the elevated SCC reflecting an increased probability of occurrence to subclinical mastitis and DRB3.2 allele *8 (p < 0.03). The results also revealed significant positive relationships of alleles*22 (p < 0.01) and allele*11 (p < 0.05) with milk fat percent as well as of alleles*24 (p < 0.03) and *22 (p < 0.05) with protein percent. The present study failed to find any association between milk yield and tested alleles. Because of the lack of consistency among results of similar studies, we suggest further investigations to determine the precise nature of these associations with the high polymorphic bovine MHC region to be performed based on haplotypes.  相似文献   

11.
The highly polymorphic genes within the major histocompatibility complex (MHC) not only play a major role in immunity resistance, but also seem to provide hints for mate choice in some animal populations. In the present study we investigated MHC‐related mate choice in a small natural population (group size 40–55 individuals) of a polygynous primate, the Sichuan snub‐nosed monkey (Rhinopithecus roxellana). We found that there was no evidence either for MHC‐disassortative mating, or for females to mate with males based on MHC heterozygosity or specific alleles. Nevertheless, of the 11 alleles identified, we found that the frequencies of 2 alleles, Rhro‐DRB2 (P < 0.01) and Rhro‐DRB5 (P < 0.05) were higher in offspring than in their parents. These findings suggest that MHC‐DRB in this population of R. roxellana is unlikely to be associated with mating preferences. Limited female opportunities for mate choice are likely due, in part, to the harem breeding structure present in R. roxellana, and the relatively small number of resident adult males in our study band (N = 4–6). In addition, we suggest that differences in the frequency of particular alleles across generations may be linked to parasite resistance in a fluctuating environment; however, confirmation of this finding requires further study.  相似文献   

12.
Diversity of the ovine DQA2 gene   总被引:6,自引:0,他引:6  
Variation in the ovine DQA2 gene was investigated in approximately 2,000 sheep from six breeds. Fragments of DNA containing the ovine DQA2 exon 2 were amplified using PCR. Single-strand conformational polymorphism analysis and DNA sequence analysis were employed to detect genetic variation. Twenty-three nucleic acid sequences, encoding 22 DQA2 amino acid sequences, were identified. This increases the number of alleles identified from 10 to 23. In some cases, three or four unique sequences were isolated from individual sheep, suggesting that these DQA2 sequences may represent two loci. Phylogenetic tree analysis revealed that 5 of these 23 sequences were more closely related to cattle DQA3 or DQA4 sequences than to other sheep DQA2 sequences. These sequences clustered together and were called DQA2-like to differentiate them from other DQA2 sequences. There was no evidence of DQA5-like sequences in sheep. Information theory-based analysis indicated that some of the DQA2-like sequences had low information content at splice sites, suggesting that these alleles may have low functional activity. Allelic lineages were observed not only at the DQA2 locus, but also at the DQA2-like locus, supporting the trans-species mode of evolution of MHC genes. Comparison of the allelic sequences suggests that polymorphism seems to have arisen largely by point mutation and gene conversion, and a recent gene conversion event seems to have occurred between the DQA2 and DQA2-like loci. The high level of sequence polymorphism detected and varied number of loci demonstrate the extensive diversity of the ovine DQA2 gene.  相似文献   

13.
14.
基于RT-PCR方法,扩增了用于马传染性贫血病毒(Equine infectious anemia virus,EIAV)减毒疫苗株CTL表位研究的5匹马的编码经典MHC-I类分子的大部分基因,具体包括编码肽结合区大部分区域、α3区、穿膜区及胞浆区蛋白的基因,并进行了PCR产物的克隆和测序。试验马匹外周血单个核细胞(Peripheral blood mono-nuclear cells,PBMC)的总RNA提取物经RT-PCR扩增,并将所得产物进行T-A克隆。从每匹马的所有克隆中,分别随机挑取鉴定为阳性重组质粒的21~23个克隆用于测序分析。研究结果表明,5匹试验马匹各自具有3~5个等位基因,由于MHC-I分子等位基因表达的共显性特征,可以推测马的基因组内可能存在2~3个基因座对应于这些等位基因,这与国外已有研究结论基本一致。另外,不同马匹PBMC表达的MHC-I类分子的差别水平不一致。除了6号与7号和10号马之间MHC-I类分子的差异较大,无相同或高度相近的经典MHC-I类分子序列外,各马匹间均表达具有1个或1个以上的相同或高度同源的对应经典的MHC-I类分子的mRNA。以上研究结果既可作为正在开展的EIAV减毒疫苗株CTL表位研究的基础性、支持性数据,又可进一步丰富国内马的经典MHC-I分子多态性方面的相关研究。  相似文献   

15.
16.
Two bovine MHC class II alleles, BoLA-DRB3*0201 and BoLA-DRB3*3301, contain a three base pair deletion which results in the deletion of a lysine (K beta 65) in the antigen recognition site (ARS). Modelling of BoLA-DRB3*0201 with the conserved lysine K beta 65 and BoLA-DRB3*0201 without K beta 65 indicated that this deletion altered the peptide specificity of the ARS, and may impact on the immune response. To test this hypothesis, the presence of K beta 65 was analysed in a sample of cattle vaccinated with the commercial cattle tick vaccine (TickGARD). Homozygous deletion of K beta 65 was significantly associated with high response to TickGARD (P<0.05). Screening of the TickGARD antigen identified a potential T cell epitope that is recognised better by animals that are homozygous for the K beta 65 deletion. This study provides evidence that changes in the ARS of MHC class II molecules may be associated with the well recognised animal to animal variation in magnitude of vaccine response.  相似文献   

17.
不同中外猪种对疾病的抵抗能力有一定差异,原因之一是不同猪种猪白细胞抗原(swine leukocyte antigen,SLA)分子的多样性不同。本研究旨在探究中外猪种的SLA基因差异,为阐明地方猪的抗病机理提供重要参考。本研究首先对健康的8头民猪以及4头大白猪进行基因组重测序,并对所获得的SNP进一步质控用于后续分析。使用VCFtools、GEVALT软件分析SLAⅠ类基因的SNP以及单倍型,并将SNP利用ENSEMBL中的VEP工具进行注释,在全局层面阐述两个猪种的SLAⅠ类基因多样性。通过Mega软件比对两猪种的经典SLAⅠ类基因外显子2和3的核苷酸及编码氨基酸序列,利用Expasy服务器上的ProtParam工具和Protscale程序分析蛋白质特性,并利用DnaSP软件计算核苷酸多样性,分析两个猪种经典SLAⅠ类基因抗原递呈能力的差异。结果表明,民猪的SLAⅠ类基因具有更多的SNPs和长度较短的单倍型块,并且错义突变的碱基数量较多。在经典SLAⅠ类基因的外显子2和3可分别鉴定出2个等位基因,民猪在等位基因上的核苷酸多样性要明显高于大白猪,并且民猪具有更多的碱基突变以及位于抗原结合位点上的氨基酸突变。两个猪种的经典SLAⅠ类基因氨基酸表现为亲水性,民猪的亲水性要强于大白猪。综上所述,SLAⅠ类基因在民猪上有更强的多态性。民猪经典SLAⅠ类基因的碱基突变数量和抗原结合位点上氨基酸突变的数量都要多于大白猪。本研究所检测到的民猪在经典SLAⅠ类基因ARSs上的变异可为猪抗病育种标记的筛选提供参考。  相似文献   

18.
The availability of a panel of monoclonal antibodies to sheep MHC class I and class II gene products has allowed for the first time an assessment of the relative complexity of the sheep MHC. By using four monoclonal antibodies to MHC class I, and seven monoclonal antibodies to MHC class II molecules together with one-dimensional SDS-PAGE, sequential immunoprecipitation and 2-dimensional gel analysis, three class I gene products and four distinct subsets of class II molecules have been identified. Sheep class I molecules showed heterogeneity on 2-dimensional gels and as in mouse and man, represented the products of at least three different non-allelic class I genes. Interestingly, the sheep beta 2 microglobulin molecule also displayed heterogeneity, consistent with either two primary gene products or allelic variation. Four sheep class II monoclonal antibodies identified distinct, non-overlapping subsets of sheep class II molecules of Mr 32-36 K (alpha chain) and 25-28 K (beta chain). These class II molecules were co-expressed on sheep B lymphocytes and represented the primary products of different sheep MHC class II genes. The class II molecules within three of these subsets displayed allelic polymorphism essentially restricted to their beta polypeptides, while the fourth subset of class II molecules showed allelic variation in both their alpha and beta polypeptides. The results of this study represent the first evidence for gene duplication and heterogeneity within the sheep MHC. The identification of three primary class I gene products and four distinct subsets of class II molecules suggests three class I loci and up to four distinct class II subregions within the sheep MHC. Potentially large numbers of allelic variants of these different gene products may be expressed in normal sheep.  相似文献   

19.
The major histocompatibility complex (MHC) is a genetic region that has been intensively studied for the past 2 decades. Interest in the MHC has been high because of (i) the particular involvement of the MHC in transplantation reactions, including organ allograft rejection in human beings; and (ii) the more general role of MHC gene products in the genetic control of immune responses in all mammals. The MHC has several remarkable properties that include a distinctive genetic structure which has been well-preserved through evolution, and the extreme plasticity of form of the principal MHC genes, which can coexist within a single species in 30 or more allelic forms. The genes of the MHC regulate cell-cell interactions of various types within the lymphoreticular system, and thus function as the so-called "immune response" genes that have been described in mice, rats, and guinea pigs. In human beings, the "disease associations" demonstrated between MHC alleles and various pathologic conditions are probably manifestations of abnormal functions of immune regulation governed by the MHC. Studies of the MHC in domestic species are still in their infancy. However, investigations of the MHC have been carried out in swine, cattle, horses, sheep, goats, dogs, and chickens. Further research on the MHC of domestic animals is merited, both for its contribution to the overall understanding of the biological significance of the MHC and for its practical application in clinical veterinary medicine.  相似文献   

20.

Background

Hybridization between closely related wild and domestic species is of great concern because it can alter the evolutionary integrity of the affected populations. The high allelic variability of Major Histocompatibility Complex (MHC) loci usually excludes them from being used in studies to detect hybridization events. However, if a) the parental species don’t share alleles, and b) one of the parental species possesses an exceptionally low number of alleles (to facilitate analysis), then even MHC loci have the potential to detect hybrids.

Results

By genotyping the exon2 of the MHC class II DRB1 locus, we were able to detect hybridization between domestic goats (Capra hircus) and free-ranging Iberian ibex (Capra pyrenaica hispanica) by molecular means.

Conclusions

This is the first documentation of a Capra pyrenaica × Capra hircus hybridization, which presented us the opportunity to test the applicability of MHC loci as new, simple, cost-effective, and time-saving approach to detect hybridization between wild species and their domesticated relatives, thus adding value to MHC genes role in animal conservation and management.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号