Further diversity of the 5′ promoter region of the <scp>MHC</scp> class I‐related chain B gene

Laza-Briviesca, Raquel; Pearson, Hugh A.; Madrigal, J. Alejandro; Cox, S.T.

doi:10.1111/iji.12246

Cited by 3 publications

(2 citation statements)

References 13 publications

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“…The MICA promoter that is found in association with the vast majority of MICA coding alleles is MICA-P7 and had highest RRR of all promoter types except MICA-P14. MICA-P14 was found uniquely during this study in two individual UCB samples from our cohort of 181 and is described in more detail elsewhere ( 29 ). Transcriptional activity of this promoter is high, around 75% relative to the SV40 control and higher than all other MICA promoters studied.…”

Section: Resultsmentioning

confidence: 62%

“…Although the population frequency of this promoter type is largely unknown, one study investigating MICA allele and promoter haplotypes suggested an AF for MICA-P6 of around 3% in Chinese Han, on the same haplotype as MICA*008:01 ( 15 ). MICA-P13 and MICA-P14 were identified as a novel promoter types in our cohort of cord blood samples ( 29 ) and have the accession numbers KM358317 and KM358136, respectively. Although we cannot confirm the MICA allele haplotype association with MICA-P14, both individuals with this novel promoter were typed as MICA*008 so it is possible that this allele can be over-expressed in the presence of strong promoters such as P14.…”

Section: Discussionmentioning

confidence: 99%

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Functional Characterisation and Analysis of the Soluble NKG2D Ligand Repertoire Detected in Umbilical Cord Blood Plasma

et al. 2018

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We previously reported that cord blood plasma (CBP) contains significantly more soluble NKG2D ligands (sNKG2DLs), such as sMICB and sULBP1, than healthy adult plasma. Viral infection or malignant transformation upregulates expression of NKG2D ligand on affected cells, leading to NK group 2, member D (NKG2D)-mediated natural killer (NK) cell lysis. Conversely, sNKG2DL engagement of NKG2D decreases NK cell cytotoxicity leading to viral or tumour immune escape. We hypothesised that sNKG2DLs detected in CBP may represent an additional fetal–maternal tolerance mechanism. To further understand the role of sNKG2DL in pregnancy and individual contributions of the various ligand types, we carried out functional analysis using 181 CBP samples. To test the ability of CBP to suppress the function of NK cells in vitro, we measured expression of NKG2D, CD107a, and IFN-γ in NK cells from control donors after exposure to 181 individual CBP samples and characterised the sMICA, sMICB, and sULBP1 content of each one. Furthermore, to detect possible allelic differences between samples that may also affect function, we carried out umbilical cord blood typing for MHC class I-related chain A (MICA) and MHC class I-related chain B (MICB) coding and promoter allelic types. Strongest functional correlations related to increasing concentration of exosomal sULBP1, which was present in all CBP samples tested. In addition, common MICB alleles, such as MICB*005:02, resulted in increased concentration of sMICB. Interestingly, MICB*005:02 uniquely associated with eight different promoter types. Among promoter polymorphisms, P2 resulted in the highest expression of sMICB and P9 the least and was confirmed using luciferase reporter assays. Higher levels of sMICB associated with lower IFN-γ production, indicating that sMICB also suppressed NK cell function. We also examined the MICA functional dimorphism encoding methionine (met) or valine (val) at residue 129 associated with strong or weak NKG2D binding, respectively. Most sMICA associated with val/val, some with met/val but none with met/met and, counter-intuitively, the presence of sMICA in CBP increased NK cell cytotoxicity. We propose a model for fetal–maternal tolerance, whereby NK cell activity is limited by sULBP1 and sMICB in CBP. The release of 129val sMICA with weak NKG2D signalling may reduce the overall net suppressive signal and break tolerance thus allowing fetal NK cells to overcome immunological threats in utero.

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Section: Resultsmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Functional Characterisation and Analysis of the Soluble NKG2D Ligand Repertoire Detected in Umbilical Cord Blood Plasma

et al. 2018

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Major Histocompatibility Complex Class I Chain–Related A and B (MICA and MICB) Gene, Allele, and Haplotype Associations With Dengue Infections in Ethnic Thais

Luangtrakool

Vejbaesya

Luangtrakool

et al. 2020

The Journal of Infectious Diseases

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Background Major histocompatibility complex class I chain–related (MIC) A and B (MICA and MICB) are polymorphic stress molecules recognized by natural killer cells. This study was performed to analyze MIC gene profiles in hospitalized Thai children with acute dengue illness. Methods MIC allele profiles were determined in a discovery cohort of patients with dengue fever or dengue hemorrhagic fever (DHF) (n = 166) and controls (n = 149). A replication cohort of patients with dengue (n = 222) was used to confirm specific MICB associations with disease. Results MICA*045 and MICB*004 associated with susceptibility to DHF in secondary dengue virus (DENV) infections (odds ratio [OR], 3.22; [95% confidence interval (CI), 1.18–8.84] and 1.99 [1.07–2.13], respectively), and MICB*002 with protection from DHF in secondary DENV infections (OR, 0.41; 95% CI, .21–.68). The protective effect of MICB*002 against secondary DHF was confirmed in the replication cohort (OR, 0.43; 95% CI, .22–.82) and was stronger when MICB*002 is present in individuals also carrying HLA-B*18, B*40, and B*44 alleles which form the B44 supertype of functionally related alleles (0.29, 95% CI, .14–.60). Conclusions Given that MICB*002 is a low expresser of soluble proteins, these data indicate that surface expression of MICB*002 with B44 supertype alleles on DENV-infected cells confer a protective advantage in controlling DENV infection using natural killer cells.

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Relationship between factors contributing toward feelings of child-rearing difficulty experienced by older primiparas at one month postpartum

Watanabe

Natori

Hirata

et al. 2022

J. Jpn. Acad. Midwif.

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高年初産婦 294 人から回答があり，そのうちの有効回答 252 部(有効回答率 85.7%)を分析した。平均年齢 37.8 歳(±2.4 歳) ，最高年齢 46 歳であった。育児困難感の平均得点は 18.1±4.6 で，就労者の得点が高かった(p=.009) 。サポートの有無による差はなかった。高年初産婦の育児困難感に直接影響していた要因は，母親役割の自信 (−0.54) と育児ストレス (0.36) であった。子育てレジリエンスの上昇は，蓄積疲労(−0.33) ，育児ストレスの減少(−0.41) ，母親であることの満足感(0.31) ，母親役割の自信の向上(0.30)を介して，育児困難感を減少させた。さらに，子育てレジリエンスの上昇は夜間睡眠の充足感 (0.31) を高め，蓄積疲労を減少させる (−.

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Further diversity of the 5′ promoter region of the MHC class I‐related chain B gene

Abstract: We have now found a total of 15 individual MICB promoter sequences, varying by combination of 18 polymorphic positions within the MICB minimal promoter sequence. Sequence-based typing and cloning characterized the three new 5' promoter sequences as MICB-P13, MICB-P14 and MICB-P15.

Cited by 3 publications

References 13 publications

Functional Characterisation and Analysis of the Soluble NKG2D Ligand Repertoire Detected in Umbilical Cord Blood Plasma

Functional Characterisation and Analysis of the Soluble NKG2D Ligand Repertoire Detected in Umbilical Cord Blood Plasma

Major Histocompatibility Complex Class I Chain–Related A and B (MICA and MICB) Gene, Allele, and Haplotype Associations With Dengue Infections in Ethnic Thais

Relationship between factors contributing toward feelings of child-rearing difficulty experienced by older primiparas at one month postpartum

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