|
| |
|
|
Assessment of expression markers of HLA class II genes.
Zajacová, Marta ; Černá, Marie (advisor) ; Černý, Jan (referee)
BACKGROUND: HLA molecules play a central role in the immune response. HLA class II are involved in the selection of the T-cell repertoire in the thymus, and in presentation of antigenic peptides to antigen reactive CD4-positive T cells. The HLA class II act as restriction determinants in the presentation of antigens to T lymphocytes and their expression on the cell surface is necessary for triggering the immune responses. Regulated transcription of HLA class II genes is a complex system involving cis-acting sequence elements and trans-acting protein factors. It has been reported that allelic polymorphism exists in the regulatory regions of HLA class II DQA1, DQB1 and DRB1 genes. Most of the polymorphisms appear to be conserved within a haplotype. The hierarchy of sequence homology which exists among the structural genes is not paralleled among their promoter sequences. It is of interest that the most striking discrepancy was found for the DR4 linked alleles, DQB1*0301 and DQB1*0302, which were described as frequent risk factors for a variety of autoimmune diseases. The structural genes of these two alleles are the most closely related, but their regulatory sequences are the most heterogeneous among DQB1 variants. These sequence differences correspond to functional variation: The promoter strength...
|
|
|
Regulation of HLA class II genes expression
Zajacová, Marta ; Černá, Marie (advisor) ; Černý, Jan (referee) ; Slavčev, Antonij (referee)
HLA class II genes are known to be highly polymorphic, even in the regulatory non-coding gene regions. Polymorphism in the promoter region potentially forms a strong basis for an uneven allele-specific expression. Even though it is known that the amount of HLA class II molecules on the cell surface has a significant role in shaping immune response, HLA class II expression polymorphism has not yet been thoroughly measured. The thesis aims to shed light into allele-specific mRNA expression and promoter DNA methylation of HLA class II genes. Two studies, each addressing different aspects of the HLA class II allele expression regulation, were conducted. Study A examines the DNA methylation of 10 DQA1 promoter and its effect on the DQA1 mRNA expression. DNA methylation in whole blood cells was determined with bisulfite sequencing and mRNA expression was measured using RT-qPCR. Even though inter-allelic differences in overall methylation were observed (the most methylated alleles were DQA1*02:01 and *04:01), the expected negative correlation between the DQA1 promoter DNA methylation density and the allele expression was not observed. We suggest that the genetic polymorphism in the region (especially region upstream of position -400, which is almost completely methylated in all alleles) may lead to different...
|
|
|
Regulation of HLA class II genes expression
Zajacová, Marta ; Černá, Marie (advisor) ; Černý, Jan (referee) ; Slavčev, Antonij (referee)
HLA class II genes are known to be highly polymorphic, even in the regulatory non-coding gene regions. Polymorphism in the promoter region potentially forms a strong basis for an uneven allele-specific expression. Even though it is known that the amount of HLA class II molecules on the cell surface has a significant role in shaping immune response, HLA class II expression polymorphism has not yet been thoroughly measured. The thesis aims to shed light into allele-specific mRNA expression and promoter DNA methylation of HLA class II genes. Two studies, each addressing different aspects of the HLA class II allele expression regulation, were conducted. Study A examines the DNA methylation of 10 DQA1 promoter and its effect on the DQA1 mRNA expression. DNA methylation in whole blood cells was determined with bisulfite sequencing and mRNA expression was measured using RT-qPCR. Even though inter-allelic differences in overall methylation were observed (the most methylated alleles were DQA1*02:01 and *04:01), the expected negative correlation between the DQA1 promoter DNA methylation density and the allele expression was not observed. We suggest that the genetic polymorphism in the region (especially region upstream of position -400, which is almost completely methylated in all alleles) may lead to different...
|
|
|
Assessment of expression markers of HLA class II genes.
Zajacová, Marta ; Černá, Marie (advisor) ; Černý, Jan (referee)
BACKGROUND: HLA molecules play a central role in the immune response. HLA class II are involved in the selection of the T-cell repertoire in the thymus, and in presentation of antigenic peptides to antigen reactive CD4-positive T cells. The HLA class II act as restriction determinants in the presentation of antigens to T lymphocytes and their expression on the cell surface is necessary for triggering the immune responses. Regulated transcription of HLA class II genes is a complex system involving cis-acting sequence elements and trans-acting protein factors. It has been reported that allelic polymorphism exists in the regulatory regions of HLA class II DQA1, DQB1 and DRB1 genes. Most of the polymorphisms appear to be conserved within a haplotype. The hierarchy of sequence homology which exists among the structural genes is not paralleled among their promoter sequences. It is of interest that the most striking discrepancy was found for the DR4 linked alleles, DQB1*0301 and DQB1*0302, which were described as frequent risk factors for a variety of autoimmune diseases. The structural genes of these two alleles are the most closely related, but their regulatory sequences are the most heterogeneous among DQB1 variants. These sequence differences correspond to functional variation: The promoter strength...
|
|
| |
guest ::
RSS feed.