MICA polymorphism: biology and importance in immunity and disease

Choy, Mun-Kit; Phipps, Maude E.

doi:10.1016/j.molmed.2010.01.002

Cited by 87 publications

(100 citation statements)

References 105 publications

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“…It appeared that the genetic factor of specific haplotypes is associated with either increased or decreased risk of aGVHD. 5 The role of some of these non-HLA genes have been studied (reviewed [6][7][8][9][10] ): single nucleotide polymorphisms and/or microsatellites within cytokine (-receptor) genes and other non-HLA encoded genes, including those of the innate immune system, may indeed influence HSCT outcome. [11][12][13][14][15][16][17] Genes in the TNF block, MICA/MICB and microsatellite markers are of specific interest because they are in linkage disequilibrium (LD) with the classical HLA genes and could be inherited together as one genetic unit.…”

Section: Introductionmentioning

confidence: 99%

The impact of frequent HLA haplotypes in high linkage disequilibrium on donor search and clinical outcome after unrelated haematopoietic SCT

Jöris

Lankester

Borne

et al. 2012

Bone Marrow Transplant

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The MHC region on chromosome 6 contains a large number of non-HLA genes next to the HLA genes. Matching for HLA in unrelated hematopoietic SCT (HSCT) does not necessarily mean that these non-HLA genes are also matched. We selected 348 Northwest European patients transplanted with an HLA-A-, -B-, -C-, -DRB1-, -DQB1-matched unrelated donor (MUD) between 1987 and 2008. Patients' haplotypes were identified via descend. We were unable to determine the haplotypes of the donor; therefore we used frequent haplotypes (FH) in high linkage disequilibrium (LD) as a proxy for haplotype matching. Presence of a FH in a patient positively affected the probability and speed of identifying a matched unrelated donor. Competing risk survival analysis showed that patients with one or two FH have a statistically significantly decreased probability of developing Xgrade II acute GVDH (aGVHD) without increased risk of relapse compared to patients without FH (HR (95% CI): 0.53 (0.31-0.91)). This association was strongest for those FH with the highest LD between both HLA-A and -C or -B, and HLA-C or -B and -DRB1 (HR (95% CI): 0.49 (0.26-0.92)). These results extend evidence that non-HLA allele coding regions have a significant impact on development of Xgrade II aGVHD. We conclude that there is more to successful HSCT than matching for HLA genes.

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Section: Introductionmentioning

confidence: 99%

The impact of frequent HLA haplotypes in high linkage disequilibrium on donor search and clinical outcome after unrelated haematopoietic SCT

Jöris

Lankester

Borne

et al. 2012

Bone Marrow Transplant

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show abstract

“…MICA is a highly polymorphic molecule, with over 60 human alleles identified (52,53). Of the cells used in this study, ARPE-19 cells express the MICA*011 and -*027 alleles (G Wilkinson, Cardiff University, personal communication), while 293T cells are homozygous for the MICA*008 allele (49), the most prevalent allele in many populations (54,55).…”

Section: Discussionmentioning

confidence: 99%

Varicella-Zoster Virus and Herpes Simplex Virus 1 Differentially Modulate NKG2D Ligand Expression during Productive Infection

Campbell

McSharry

Steain

et al. 2015

J Virol

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Natural killer (NK) cell-deficient patients are particularly susceptible to severe infection with herpesviruses, especially varicellazoster virus (VZV) and herpes simplex virus 1 (HSV-1). The critical role that NK cells play in controlling these infections denotes an intricate struggle for dominance between virus and NK cell antiviral immunity; however, research in this area has remained surprisingly limited. Our study addressed this absence of knowledge and found that infection with VZV was not associated with enhanced NK cell activation, suggesting that the virus uses specific mechanisms to limit NK cell activity. Analysis of viral regulation of ligands for NKG2D, a potent activating receptor ubiquitously expressed on NK cells, revealed that VZV differentially modulates expression of the NKG2D ligands MICA, ULBP2, and ULBP3 by upregulating MICA expression while reducing ULBP2 and ULBP3 expression on the surface of infected cells. Despite being closely related to VZV, infection with HSV-1 produced a remarkably different effect on NKG2D ligand expression. A significant decrease in MICA, ULBP2, and ULBP3 was observed with HSV-1 infection at a total cellular protein level, as well as on the cell surface. We also demonstrate that HSV-1 differentially regulates expression of an additional NKG2D ligand, ULBP1, by reducing cell surface expression while total protein levels are unchanged. Our findings illustrate both a striking point of difference between two closely related alphaherpesviruses, as well as suggest a powerful capacity for VZV and HSV-1 to evade antiviral NK cell activity through novel modulation of NKG2D ligand expression. IMPORTANCEPatients with deficiencies in NK cell function experience an extreme susceptibility to infection with herpesviruses, in particular, VZV and HSV-1. Despite this striking correlation, research into understanding how these two alphaherpesviruses interact with NK cells is surprisingly limited. Through examination of viral regulation of ligands to the activating NK cell receptor NKG2D, we reveal patterns of modulation by VZV, which were unexpectedly varied in response to regulation by HSV-1 infection. Our study begins to unravel the undoubtedly complex interactions that occur between NK cells and alphaherpesvirus infection by providing novel insights into how VZV and HSV-1 manipulate NKG2D ligand expression to modulate NK cell activity, while also illuminating a distinct variation between two closely related alphaherpesviruses. V aricella-zoster virus (VZV) and herpes simplex virus type 1 (HSV-1) are two medically important human alphaherpesviruses that cause widespread disease in human hosts. VZV is the causative agent of varicella (chickenpox) and herpes zoster (shingles), while HSV-1 causes recurrent orofacial herpes infection and, in severe cases, encephalitis. Despite manifestation as distinct diseases, these two viruses share a high degree of homology in the structures of their genomes and encode many similar proteins, as well as employ extensive immune evasion strat...

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“…72 Soluble MICA shed by tumor cells can bind to NKG2D receptor on NK and T cells without triggering downstream signals and induce degradation of the NKG2D receptor on the immune effector cells. 73 Internalization of the complex also may result in expansion of immunosuppressive NKG2D + CD4 + T cells. There are potentially ligand-receptor interactions other than NKG2D that may also contribute to suppression of proliferating T cells.…”

Section: Class I-like Genes: Mica/micbmentioning

confidence: 99%

Survival of the fittest or best adapted: HLA-dependent tumor development

Masucci

Andersson

Villabona

et al. 2010

J Nucleic Acids Invest

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The major histocompatibility complex (MHC) comprises a set of genes that are critical to immunity and surveillance against neoplastic transformation. There is increasing evidence that the MHC antigens not only regulate antitumor immune responses in experimental animal models but directly correlate with survival and prognosis of patients with diverse types of cancers. MHC antigens may in the future function as potential biomarkers for prognosis and allow selection of cancer patients for intensive therapy.

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MICA polymorphism: biology and importance in immunity and disease

Cited by 87 publications

References 105 publications

The impact of frequent HLA haplotypes in high linkage disequilibrium on donor search and clinical outcome after unrelated haematopoietic SCT

The impact of frequent HLA haplotypes in high linkage disequilibrium on donor search and clinical outcome after unrelated haematopoietic SCT

Varicella-Zoster Virus and Herpes Simplex Virus 1 Differentially Modulate NKG2D Ligand Expression during Productive Infection

Survival of the fittest or best adapted: HLA-dependent tumor development

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