Ena-DATASET-GIS-01-08-2018-10:48:03:309-1391 - samples
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ABSTRACT:
PROVIDER: EGAD00001004265 | EGA |
REPOSITORIES: EGA
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Project description:BackgroundHLA-E interaction with inhibitory receptor, NKG2A attenuates NK-mediated cytotoxicity. NKG2A overexpression by SARS-CoV-2 exhausts NK cells function, whereas virus-induced down-regulation of MHC-Ia reduces its derived-leader sequence peptide levels required for proper binding of HLA-E to NKG2A. This leads HLA-E to become more complex with viral antigens and delivers them to CD8+ T cells, which facilitates cytolysis of infected cells. Now, the fact that alleles of HLA-E have different levels of expression and affinity for MHC Ia-derived peptide raises the question of whether HLA-E polymorphisms affect susceptibility to COVID-19 or its severity.Methods104 COVID-19 convalescent plasma donors with/without history of hospitalization and 18 blood donors with asymptomatic COVID-19, all were positive for anti-SARS-CoV-2 IgG antibody as well as a group of healthy control including 68 blood donors with negative antibody were subjected to HLA-E genotyping. As a privilege, individuals hadn't been vaccinated against COVID-19 and therefore naturally exposed to the SARS-CoV-2.ResultsThe absence of HLA-E*01:03 allele significantly decreases the odds of susceptibility to SARS-CoV-2 infection [p = 0.044; OR (95 %CI) = 0.530 (0.286 - 0.983)], suggesting that HLA-E*01:01 + HLA-E*01:01 genotype favors more protection against SARS-CoV-2 infection. HLA-E*01:03 + HLA-E*01:03 genotype was also significantly associated with more severe COVID-19 [p = 0.020; 2.606 (1.163 - 5.844) CONCLUSION: Here, our observation about lower susceptibility of HLA-E*01:01 + HLA-E*01:01 genotype to COVID-19 could be clinical evidence in support of some previous studies suggesting that the lower affinity of HLA-E*01:01 to peptides derived from the leader sequence of MHC class Ia may instead shift its binding to virus-derived peptides, which then facilitates target recognition by restricted conventional CD8+ T cells and leads to efficient cytolysis. On the other hand, according to other studies, less reactivity of HLA-E*01:01 with NKG2A abrogates NK cells or T cells inhibition, which may also lead to a greater cytotoxicity against SARS-CoV-2 infected cells compared to HLA-E*01:03. Taken together given HLA-E polymorphisms, the data presented here may be useful in identifying more vulnerable individuals to COVID-19 for better care and management. Especially since along with other risk factors in patients, having HLA-E*01:03 + HLA-E*01:03 genotype may also be associated with the possibility of severe cases of the disease.
| S-EPMC9922572 | biostudies-literature
Project description:BackgroundThe polymorphisms of classical HLA-Ia and HLA-II loci have been associated with Posner-Schlossman syndrome (PSS) in the southern Chinese population. However, the associations of non-classical HLA-Ib (e.g., HLA-E and HLA-G) loci with PSS have not been reported for in the southern Chinese population. This study aimed to evaluate the associations of the HLA-E and HLA-G loci with PSS in a southern Chinese Han population group.MethodsNinety-seven unrelated patients with PSS and 90 ethnically matched control subjects were recruited from the Shenzhen Eye Hospital in China. The full-length sequences of HLA-E and HLA-G genes were amplified by long-range high-fidelity PCR, and the third exon of the HLA-E gene and the coding region of the HLA-G gene were sequenced.ResultsThe allele frequency of HLA-E*01:03 in patients with PSS was significantly higher than that in the control group (P=0.017, corrected P=0.034, OR =1.66). The genotype frequencies of HLA-E*01:01/01:03 and HLA-E*01:03/01:03 in the PSS group were significantly higher than that in the control group (P=0.027, OR =2.62; P=0.011, OR =3.05; respectively). There were no significant differences in the frequency of HLA-G alleles and genotypes between the two groups (all P>0.05). The haplotype frequency of HLA-E*01:03-G*01:01 in the PSS group was significantly higher than that in the control group (P=0.019, OR =1.63), although this association did not survive the Bonferroni correction (corrected P=0.13).ConclusionsThis study proved for the first time that HLA-E*01:03 and HLA-E*01:03-G*01:01 might be risk factors for PSS.
| S-EPMC6989981 | biostudies-literature
Project description: Not available
| S-EPMC6849947 | biostudies-literature
Project description:Description not provided
| EGAD00001004048 | EGA
Project description:MHC class II molecules are composed of one α-chain and one β-chain whose membrane distal interface forms the peptide binding groove. Most of the existing knowledge on MHC class II molecules comes from the cis-encoded variants where the α- and β-chain are encoded on the same chromosome. However, trans-encoded class II MHC molecules, where the α- and β-chain are encoded on opposite chromosomes, can also be expressed. We have studied the trans-encoded class II HLA molecule DQ2.3 (DQA1*03:01/DQB1*02:01) that has received particular attention as it may explain the increased risk of certain individuals to type 1 diabetes. We report the x-ray crystal structure of this HLA molecule complexed with a gluten epitope at 3.05 Å resolution. The gluten epitope, which is the only known HLA-DQ2.3-restricted epitope, is preferentially recognized in the context of the DQ2.3 molecule by T-cell clones of a DQ8/DQ2.5 heterozygous celiac disease patient. This preferential recognition can be explained by improved HLA binding as the epitope combines the peptide-binding motif of DQ2.5 (negative charge at P4) and DQ8 (negative charge at P1). The analysis of the structure of DQ2.3 together with all other available DQ crystal structures and sequences led us to categorize DQA1 and DQB1 genes into two groups where any α-chain and β-chain belonging to the same group are expected to form a stable heterodimer.
| S-EPMC3340161 | biostudies-literature
Project description:Description not provided
| EGAD00001004408 | EGA
Project description:Description not provided
| EGAD00001001036 | EGA
Project description:Analysis of HEK293 whole cell lysates to accompany enriched taggedCaM adduct sample analysis.
2019-05-16 | MSV000083790 | MassIVE
Project description:HLA-C*03:03:01:52N differs from HLA-C*03:03:01:01 by one nucleotide substitution at position gDNA 202 (A>G) in Intron1.
| S-EPMC9542030 | biostudies-literature
Project description:Verticillium dahliae Kleb., a soil-borne fungus that colonizes vascular tissues, induces wilting, chlorosis and early senescence in potato. Difference in senescence timing found in two diploid potato clones, 07506-01 and 12120-03, was studied and genetic variation in response to V. dahliae infection was identified as a causal factor. The clone, 07506-01, was infected with V. dahliae but did not develop symptoms, indicating tolerance to the pathogen. The other diploid clone, 12120-03 had low levels of pathogen with infection and moderate symptoms indicating partial resistance. 07506-01 was found to carry two susceptible alleles of the Ve2 gene and 12120-03 carried one Ve2 resistant and one susceptible allele. Infected leaves of the two clones were compared using gene expression profiling with the Potato Oligonucleotide Chip Initiative (POCI) microrarray. The results provide further evidence for differences in response of the two clones to infection with V. dahliae. Chlorophyll biosynthesis was higher in the tolerant 07506-01 compared to partially resistant 12120-03. On the other hand, expression of fungal defense genes, Ve resistance genes and defense phytohormone biosynthetic enzyme genes was decreased in 07506-01 compared to 12120-03 suggesting defense responses were suppressed in tolerance compared to resistance. Transcription factor gene expression differences pointed to the WRKY family as potential regulators of V. dahliae responses in potato.
2013-07-15 | GSE48881 | GEO