Objective:To compare the genotype frequencies of HLA class-ⅡDRB1 alleles in Giardia(G.)lamblia-infected children.Methods:A total of 490 Egyptian children aged 2-16 years were subjected to microscopic stool examinatio...Objective:To compare the genotype frequencies of HLA class-ⅡDRB1 alleles in Giardia(G.)lamblia-infected children.Methods:A total of 490 Egyptian children aged 2-16 years were subjected to microscopic stool examination to detect G.lamblia infection,and to exclude other intestinal pathogens.On the basis of their microscopic findings,a group of 80 children were chosen as giardiasis cases,another 80 children were confirmed as Giardia free control group by immunochromatographic test,and the remaining children were excluded.Both giardiasis and control groups were then subjected to blood examination to identify their genetic type of HLA-DRB1 alleles.Results:HLA class-ⅡDRB1*03:01 and DRB1*13:01 alleles were significantly associated with G.lamblia infection(P<0.001 for each variable).On the other hand,HLA class-ⅡDRB1*04:02,DRB1*10:01,DRB1*14:01 and DRB1*15:01 alleles were significantly demonstrated in Giardia free children.However,other HLA-DRB1 alleles did not show any significant association with giardiasis.Conclusions:HLA class-ⅡDRB1*03,DRB1*13,DRB1*04,DRB1*10,DRB1*14 and DRB1*15 alleles may be involved in the establishment of host immune response to G.lamblia infection.展开更多
AIM: To elucidate the molecular mechanisms leading to development of functionally impaired dendritic cells(DCs) in chronic hepatitis C(CHC) patients infected with genotype 3 virus.METHODS: This prospective study was c...AIM: To elucidate the molecular mechanisms leading to development of functionally impaired dendritic cells(DCs) in chronic hepatitis C(CHC) patients infected with genotype 3 virus.METHODS: This prospective study was conducted on the cohorts of CHC individuals identified as responders or non-responders to antiviral therapy. Myeloid DCs were isolated from the peripheral blood of each subject using CD1c(BDCA1)+ DC isolation Kit. Monocytes from healthy donor were cultured with DC growth factors such as IL-4 and GM-CSF either in the presence or absence of hepatitis C virus(HCV) viral proteins followed by LPS stimulation. Phenotyping was done by flowcytometry and gene expression profiling was evaluated by real-time PCR.RESULTS: Non-responders [sustained virological response(SVR)-ve] to conventional antiviral therapy had significantly higher expression of genes associated with interferon responsive element such as IDO1 and PD-L1(6-fold) and negative regulators of JAK-STAT pathway such as SOCS(6-fold) as compared to responders(SVR+ve) to antiviral therapy. The downregulated genes in non-responders included factors involved in antigen processing and presentation mainly belonging to major histocompatibility complex(MHC) Class-Ⅱ family as HLA-DP, HLA-DQ(2-fold) and superoxide dismutase(2-fold). Cells grown in the presence of HCV viral proteins had genes downregulated for factors involved in innate response, interferon signaling, DC maturation and co-stimulatory signaling to T-cells, while the genes for cytokine signaling and Toll-like receptors(4-fold) were upregulated as compared to cells grown in absence of viral proteins.CONCLUSION: Underexpressed MHC class-Ⅱ genes and upregulated negative regulators in non-responders indicate diminished capacity to present antigen and may constitute mechanism of functionally defective state of DCs.展开更多
Reverse vaccinology method was used to predict the monovalent peptide vaccine candidate to produce antibodies for therapeutic purpose and to predict tetravalent vaccine candidate to act as a common vaccine to cover al...Reverse vaccinology method was used to predict the monovalent peptide vaccine candidate to produce antibodies for therapeutic purpose and to predict tetravalent vaccine candidate to act as a common vaccine to cover all the dengue virus serotypes. Envelope（E）-proteins of DENV-1-4 serotypes were used for vaccine prediction using NCBI,Uniprot/Swissprot, Swiss-prot viewer, VaxiJen V2.0, TMHMM, BCPREDS, Propred-1, Propred and MHC Pred. Eproteins of DENV-1-4 serotypes were identified as antigen from which T cell epitopes, through B cell epitopes, were predicted to act as peptide vaccine candidates. Each selected T cell epitope of E-protein was confirmed to act as vaccine and to induce complementary antibody against particular serotype of dengue virus. Chimeric tetravalent vaccine was formed by the conjugation of four vaccines, each from four dengue serotypes to act as a common vaccine candidate for all the four dengue serotypes. It can be justifiably concluded that the monovalent 9-mer T cell epitope for each DENV serotype can be used to produce specific antibody against dengue virus and a chimeric common tetravalent vaccine candidate to yield a comparative vaccine to cover any of the four dengue virus serotype. This vaccine is expected to be highly immunogenic against dengue fever.展开更多
The interaction among type Ⅱ collagen(CⅡ),human DR4 major histocompatibility complex type Ⅱ molecule(MHC Ⅱ)and T-cell receptor(TCR)is associated with the development of rheumatoid arthritis(RA).The activation of T...The interaction among type Ⅱ collagen(CⅡ),human DR4 major histocompatibility complex type Ⅱ molecule(MHC Ⅱ)and T-cell receptor(TCR)is associated with the development of rheumatoid arthritis(RA).The activation of T cells can be reduced through exposure to modified CⅡ(263-272)glycopeptide fragment via competitive inhibition with self-antigen.In this work,30 peptides based on the sequence of CⅡ(263-272)were prepared and evaluated for their binding to DR4 protein by surface plasmon resonance(SPR)assay.The effect on the secretion of pro-inflammatory factors by the spleen cells in collagen induced rheumatoid arthritis(CIA)mouse was also investigated.Two N-glycosylated CⅡ peptides were identified to have strong binding to the human recombinant DR4 protein and weak proinflammatory effect.These glycopeptides could be developed as therapeutic saccharide vaccines for the treatment of rheumatoid arthritis(RA).展开更多
文摘Objective:To compare the genotype frequencies of HLA class-ⅡDRB1 alleles in Giardia(G.)lamblia-infected children.Methods:A total of 490 Egyptian children aged 2-16 years were subjected to microscopic stool examination to detect G.lamblia infection,and to exclude other intestinal pathogens.On the basis of their microscopic findings,a group of 80 children were chosen as giardiasis cases,another 80 children were confirmed as Giardia free control group by immunochromatographic test,and the remaining children were excluded.Both giardiasis and control groups were then subjected to blood examination to identify their genetic type of HLA-DRB1 alleles.Results:HLA class-ⅡDRB1*03:01 and DRB1*13:01 alleles were significantly associated with G.lamblia infection(P<0.001 for each variable).On the other hand,HLA class-ⅡDRB1*04:02,DRB1*10:01,DRB1*14:01 and DRB1*15:01 alleles were significantly demonstrated in Giardia free children.However,other HLA-DRB1 alleles did not show any significant association with giardiasis.Conclusions:HLA class-ⅡDRB1*03,DRB1*13,DRB1*04,DRB1*10,DRB1*14 and DRB1*15 alleles may be involved in the establishment of host immune response to G.lamblia infection.
基金Supported by Council of Scientific and Industrial Research,No.27(0262)12/EMR-II
文摘AIM: To elucidate the molecular mechanisms leading to development of functionally impaired dendritic cells(DCs) in chronic hepatitis C(CHC) patients infected with genotype 3 virus.METHODS: This prospective study was conducted on the cohorts of CHC individuals identified as responders or non-responders to antiviral therapy. Myeloid DCs were isolated from the peripheral blood of each subject using CD1c(BDCA1)+ DC isolation Kit. Monocytes from healthy donor were cultured with DC growth factors such as IL-4 and GM-CSF either in the presence or absence of hepatitis C virus(HCV) viral proteins followed by LPS stimulation. Phenotyping was done by flowcytometry and gene expression profiling was evaluated by real-time PCR.RESULTS: Non-responders [sustained virological response(SVR)-ve] to conventional antiviral therapy had significantly higher expression of genes associated with interferon responsive element such as IDO1 and PD-L1(6-fold) and negative regulators of JAK-STAT pathway such as SOCS(6-fold) as compared to responders(SVR+ve) to antiviral therapy. The downregulated genes in non-responders included factors involved in antigen processing and presentation mainly belonging to major histocompatibility complex(MHC) Class-Ⅱ family as HLA-DP, HLA-DQ(2-fold) and superoxide dismutase(2-fold). Cells grown in the presence of HCV viral proteins had genes downregulated for factors involved in innate response, interferon signaling, DC maturation and co-stimulatory signaling to T-cells, while the genes for cytokine signaling and Toll-like receptors(4-fold) were upregulated as compared to cells grown in absence of viral proteins.CONCLUSION: Underexpressed MHC class-Ⅱ genes and upregulated negative regulators in non-responders indicate diminished capacity to present antigen and may constitute mechanism of functionally defective state of DCs.
基金the DST-SERB (SB/YS/ LS-109/2014) for providing financial assistance in this projectthe management of A.V.V.M.Sri Pushpam College (Autonomous), Poondi,for providing them necessary facilities and support to carry out this work
文摘Reverse vaccinology method was used to predict the monovalent peptide vaccine candidate to produce antibodies for therapeutic purpose and to predict tetravalent vaccine candidate to act as a common vaccine to cover all the dengue virus serotypes. Envelope（E）-proteins of DENV-1-4 serotypes were used for vaccine prediction using NCBI,Uniprot/Swissprot, Swiss-prot viewer, VaxiJen V2.0, TMHMM, BCPREDS, Propred-1, Propred and MHC Pred. Eproteins of DENV-1-4 serotypes were identified as antigen from which T cell epitopes, through B cell epitopes, were predicted to act as peptide vaccine candidates. Each selected T cell epitope of E-protein was confirmed to act as vaccine and to induce complementary antibody against particular serotype of dengue virus. Chimeric tetravalent vaccine was formed by the conjugation of four vaccines, each from four dengue serotypes to act as a common vaccine candidate for all the four dengue serotypes. It can be justifiably concluded that the monovalent 9-mer T cell epitope for each DENV serotype can be used to produce specific antibody against dengue virus and a chimeric common tetravalent vaccine candidate to yield a comparative vaccine to cover any of the four dengue virus serotype. This vaccine is expected to be highly immunogenic against dengue fever.
基金supported by the National Natural Science Foundation of China(Nos.81930097,21977005,82151223)supported by the National Key R&D Program of China(No.2022YFF1203005).
文摘The interaction among type Ⅱ collagen(CⅡ),human DR4 major histocompatibility complex type Ⅱ molecule(MHC Ⅱ)and T-cell receptor(TCR)is associated with the development of rheumatoid arthritis(RA).The activation of T cells can be reduced through exposure to modified CⅡ(263-272)glycopeptide fragment via competitive inhibition with self-antigen.In this work,30 peptides based on the sequence of CⅡ(263-272)were prepared and evaluated for their binding to DR4 protein by surface plasmon resonance(SPR)assay.The effect on the secretion of pro-inflammatory factors by the spleen cells in collagen induced rheumatoid arthritis(CIA)mouse was also investigated.Two N-glycosylated CⅡ peptides were identified to have strong binding to the human recombinant DR4 protein and weak proinflammatory effect.These glycopeptides could be developed as therapeutic saccharide vaccines for the treatment of rheumatoid arthritis(RA).
