Identification of MICA as a new polymorphic alloantigen recognized by antibodies in sera of organ transplant recipients

Zwirner, Norberto Walter; Marcos, C. Y.; Mirbaha, Fariba; Zou, Yizhou; Šťastný, Peter

doi:10.1016/s0198-8859(00)00162-2

Cited by 171 publications

(130 citation statements)

References 7 publications

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“…However, it is well known that NKG2D ligands display a great degree of polymorphism both in mice (46) and humans (47). Thus, to develop a widely applicable cancer vaccine, it should be determined whether an allogeneic NKG2D ligand can also serve as an adjuvant for DNA vaccines.…”

Section: Discussionmentioning

confidence: 99%

DNA-based vaccines activate innate and adaptive antitumor immunity by engaging the NKG2D receptor

Zhou

Luo

Lo³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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The interaction of NKG2D, a stimulatory receptor expressed on natural killer (NK) cells and activated CD8 ؉ T cells, and its ligands mediates stimulatory and costimulatory signals to these cells. Here, we demonstrate that DNA-based vaccines, encoding syngeneic or allogeneic NKG2D ligands together with tumor antigens such as survivin or carcinoembryonic antigen, markedly activate both innate and adaptive antitumor immunity. Such vaccines result in highly effective, NK؊ and CD8 ؉ T cell-mediated protection against either breast or colon carcinoma cells in prophylactic and therapeutic settings. Notably, this protection was irrespective of the NKG2D ligand expression level of the tumor cells. Hence, this strategy has the potential to lead to widely applicable and possibly clinically useful DNA-based cancer vaccines.NK cells ͉ NKG2D ligands ͉ T cells ͉ survivin ͉ Peyer's patches

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Section: Discussionmentioning

confidence: 99%

DNA-based vaccines activate innate and adaptive antitumor immunity by engaging the NKG2D receptor

Zhou

Luo

Lo³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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“…11,12 The peptide, designated Z167, (MNVRNFLKEDAMKTKTHYHAM) was conjugated to KLH at a 1:1 (w/w) ratio using 0.2% (4 ll/ml) glutaraldehyde for 1 hr at room temperature, with constant agitation. The conjugated peptide was then dialyzed against PBS.…”

Section: Generation Of Anti-mica Antibodymentioning

confidence: 99%

Expression of the stress-related MHC class I chain-related protein MICA is an indicator of good prognosis in colorectal cancer patients

Watson¹,

Spendlove²,

Madjd³

et al. 2005

Int. J. Cancer

134

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The realization of targeted cancer therapy has driven the need to improve selection of patients with colorectal cancer for adjuvant therapy, leading to a search for potential new prognostic markers. There is accumulating evidence that immunosurveillance acts as an extrinsic tumor suppressor. As genetic instability is an early event in colorectal cancer, this can lead to altered expression of molecules conferring resistance to immune attack. Hence, molecules up or downregulated in this process may impact on patient survival. In our study, 449 colorectal tumors were screened for expression of the stress-related protein MICA, which functions as a ligand for the NKG2D receptor and whose expression confers susceptibility to both T-and NK-cell attack. Intensity of MICA expression was quantified using automated image analysis and MICA expression showed no correlation with conventional clinicopathological variables. In contrast, survival analysis showed a significant correlation between higher levels of MICA expression and improved disease-specific survival, with independent prognostic significance in multivariate analysis. Thus, patients with low levels of MICA and a poor prognosis may be good candidates for aggressive chemotherapy. In contrast, patients with high expression of MICA may be candidates for the antibody therapies, as they should be susceptible to NK killing by antibody dependent cellular cytotoxicity. ' 2005 Wiley-Liss, Inc.

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“…5 MICA antigens are polymorphic and elicit antibody production after solid organ transplantation, which may be associated with organ allograft rejection. 6,7 MICA products are expressed constitutively in gut epithelium, endothelial cells, and fibroblasts and induced by stress in other cell types. 2,8,9 Because MICA gene products are augmented by stress in epithelia 10 and are recognized by a subpopulation of intestinal ␥␦ T cells, 11 they may play a role in triggering aGVHD.…”

Section: Introductionmentioning

confidence: 99%

Donor-recipient mismatches in MHC class I chain-related gene A in unrelated donor transplantation lead to increased incidence of acute graft-versus-host disease

Parmar

Lima

Zou

et al. 2009

Blood

Self Cite

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The polymorphic products of major histocompatibility complex class I-related chain A (MICA) genes are important in solid organ transplantation rejection. MICA expression is limited to gut epithelium and may play a role in triggering acute graft-versus-host disease (aGVHD). A total of 236 recipients of unrelated donor transplantation were studied. Donor-recipient human leukocyte antigen (HLA) match was 10/10 human leukocyte antigen (HLA-A, -B, -C, -DRB1, -DQB1) in 73% and MICA mismatch in 8.4%. Because of physical vicinity of the loci, MICA mismatch was significantly associated with mismatch at HLA-B and HLA-C. A higher rate of grade II-IV aGVHD was seen in MICA-mismatched patients (80% vs 40%, P ‫؍‬ .003) irrespective of degree of HLA matching (HLA 10/10 match: 75% vs 39%, P ‫؍‬ .02) and HLA any mismatch (83% vs 46%, P ‫؍‬ .003). The rate of grade II-IV gastrointestinal aGVHD was also higher in MICA-mismatched patients (35% vs 17%, P ‫؍‬ .05). We conclude that MICA may represent novel a transplantation antigen recognized by human allogeneic T cells. This study was registered at ClinicalTrials.gov (Identifier NCT00506922).

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Identification of MICA as a new polymorphic alloantigen recognized by antibodies in sera of organ transplant recipients

Cited by 171 publications

References 7 publications

DNA-based vaccines activate innate and adaptive antitumor immunity by engaging the NKG2D receptor

DNA-based vaccines activate innate and adaptive antitumor immunity by engaging the NKG2D receptor

Expression of the stress-related MHC class I chain-related protein MICA is an indicator of good prognosis in colorectal cancer patients

Donor-recipient mismatches in MHC class I chain-related gene A in unrelated donor transplantation lead to increased incidence of acute graft-versus-host disease

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