The DBY gene codes for an HLA-DQ5–restricted human male-specific minor histocompatibility antigen involved in graft-versus-host disease

Vogt, Monica; Muijsenberg, Joost W. van den; Goulmy, Els; Spierings, Eric; Kluck, P. M. C.; Kester, Michel G.D.; Soest, Ronald A. van; Drijfhout, Jan W.; Willemze, R.; Falkenburg, J.H. Frederik

doi:10.1182/blood.v99.8.3027

Cited by 145 publications

(104 citation statements)

References 32 publications

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“…The DBY gene encodes a MHC Class II antigen that is recognized by lymphocytes and involved in graft rejection. The DBX protein was not recognized by lymphocytes (Vogt et al, 2002). DBY is expressed ubiquitously in male tissues.…”

Section: Sex Chromosome Linked Gene Expressionmentioning

confidence: 88%

Gender-Specific Gene Expression in Post-Mortem Human Brain: Localization to Sex Chromosomes

Vawter

Evans

Choudary

et al. 2003

Neuropsychopharmacol

198

151

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Gender differences in brain development and in the prevalence of neuropsychiatric disorders such as depression have been reported. Gender differences in human brain might be related to patterns of gene expression. Microarray technology is one useful method for investigation of gene expression in brain. We investigated gene expression, cell types, and regional expression patterns of differentially expressed sex chromosome genes in brain. We profiled gene expression in male and female dorsolateral prefrontal cortex, anterior cingulate cortex, and cerebellum using the Affymetrix oligonucleotide microarray platform. Differentially expressed genes between males and females on the Y chromosome (DBY, SMCY, UTY, RPS4Y, and USP9Y) and X chromosome (XIST) were confirmed using real-time PCR measurements. In situ hybridization confirmed the differential expression of gender-specific genes and neuronal expression of XIST, RPS4Y, SMCY, and UTY in three brain regions examined. The XIST gene, which silences gene expression on regions of the X chromosome, is expressed in a subset of neurons. Since a subset of neurons express gender-specific genes, neural subpopulations may exhibit a subtle sexual dimorphism at the level of differences in gene regulation and function. The distinctive pattern of neuronal expression of XIST, RPS4Y, SMCY, and UTY and other sex chromosome genes in neuronal subpopulations may possibly contribute to gender differences in prevalence noted for some neuropsychiatric disorders. Studies of the protein expression of these sexchromosome-linked genes in brain tissue are required to address the functional consequences of the observed gene expression differences.

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Section: Sex Chromosome Linked Gene Expressionmentioning

confidence: 88%

Gender-Specific Gene Expression in Post-Mortem Human Brain: Localization to Sex Chromosomes

Vawter

Evans

Choudary

et al. 2003

Neuropsychopharmacol

198

151

View full text Add to dashboard Cite

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“…An association between GVHD and presence of cytotoxic T cells was found in a woman who rejected bone marrow from a male donor. [20][21][22][23] Thus it seems reasonable to conclude that H-Y antigens are responsible both for eliciting a stronger graft vs myeloma effect in male patients with a female donor than with a male donor, and the concomitant higher GVHD related mortality in this donor-patient combination. By decreasing overall transplant-related mortality with improved methods of preventing transplant-related complications during the years from 1994, it has been possible to unmask the lower REL, translating into a significantly better survival in this group as compared to the earlier time period.…”

Section: Discussionmentioning

confidence: 99%

“…14 Various reasons for the disparity in outcome have been discussed, and in some studies there has been an influence only on transplantrelated mortality, while in others there has been a difference in REL. The recent findings of minor histocompatibility antigens encoded by genes on the Y chromosomes and their possible importance in a graft vs tumor effect [20][21][22][23][24][25] was an additional reason to perform the present study. We have now investigated 1312 patients reported to the EBMT on so-called MED-B forms (complete data set) transplanted with HLA-matched sibling donors in an attempt to delineate the importance of donor gender in transplantation of patients with multiple myeloma.…”

Section: Plantationmentioning

confidence: 99%

The impact of donor gender on outcome of allogeneic hematopoietic stem cell transplantation for multiple myeloma: reduced relapse risk in female to male transplants

Gahrton

Iacobelli

Apperley

et al. 2005

Bone Marrow Transplant

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“…12 JBB4 was demonstrated to recognize the malespecific mHag DBY in the context of HLA-DQ5. 28 The T-cell clone produced both IFNg and IL-4 after antigenspecific stimulation and exerted specific cytolytic activity against targets expressing DBY in the context of HLA-DQ5. 12 T-cell clones were cultured in Iscove's modified Dulbecco's medium (IMDM) (BioWhittaker, Verviers, Belgium) containing 10% pooled human serum and 100 IU/ml IL-2 (Chiron, Amsterdam, The Netherlands).…”

Section: T-cell Clonesmentioning

confidence: 99%

“…As a model, we redirected human peripheral-blood-derived T cells by retroviral transfer of an HLA class II restricted TCR specific for the mHag dead box RNA helicase Y (DBY). 28 We generated TCR-transferred CD4 + T-cell clones that exerted specific cytolytic activity against DBY expressing EBV-LCL, and expanded specifically upon antigenspecific stimulation. Furthermore, the TCR-transferred CD4 + T-cell clones produced high amounts of cytokines upon DBY-specific stimulation.…”

mentioning

confidence: 99%

HLA class II restricted T-cell receptor gene transfer generates CD4+ T cells with helper activity as well as cytotoxic capacity

et al. 2005

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Both cytotoxic T cells and helper T cells are important in immune responses against pathogens and malignant cells.In hematological malignancies which express HLA class II molecules, immunotherapy may be directed to HLA class II restricted antigens. We investigated whether it is possible to engineer HLA class II restricted T cells with both antigenspecific cytolytic activity and the capacity to produce high amounts of cytokines. CD4 + and CD8 + peripheral-bloodderived T cells were retrovirally transduced with the HLA class II restricted minor histocompatibility antigen dead box RNA helicase Y (DBY)-specific TCR. The TCR-transduced CD4 + T cells exerted DBY-specific cytolytic activity, produced Th0, Th1, or Th2 cytokines, and proliferated upon DBY-specific stimulation. TCR-transduced CD8 + T cells exerted cytolytic activity which equaled the level of cytolytic activity of the TCR-transferred CD4 + T cells. Cotransfer of CD4 enhanced the cytolytic activity of the TCR-transduced CD8 + T cells, but introduction of CD4 was not sufficient to generate DBY-specific CD8 + T cells with the capacity to produce high amounts of cytokines. In this study, we demonstrated the feasibility to engineer T cells with antigen-specific cytolytic activity, as well as the ability to produce significant amounts of cytokines, by TCR transfer to CD4 + T cells. Gene Therapy (2005) IntroductionPatients relapsing from leukemia after allogeneic stem cell transplantation can successfully be treated by donor lymphocyte infusions (DLI), due to the graft-versusleukemia (GVL) response of the donor-derived T cells. [1][2][3][4] However, DLI is also associated with graft-versus-hostdisease (GVHD). Several studies have illustrated that depletion of CD8 + T cells from the DLI may preserve the beneficial GVL reactivity without the induction of GVHD, indicating that the CD4 + T lymphocytes may play an essential role in the antileukemic reactivity. [5][6][7][8][9][10] The mechanism by which the CD4 + T cells contribute to the GVL response is, however, not known. CD4 + T cells have been suggested to elicit the antileukemic response via the induction of minor histocompatibility antigen (mHag)-specific CD8 + T cells. 5 In addition, mHag-specific CD4 + T-helper cells have been reported to mature dendritic cells and enhance the expansion of mHag-specific cytotoxic T lymphocytes in vitro. 11 Alternatively, we have demonstrated that CD4 + T cells are capable of exerting direct cytolytic activity against leukemic cells. [12][13][14] Cellular immunotherapeutic approaches based on the adoptive transfer of T lymphocytes may require large cell numbers. Large numbers of T cells with a defined antigen specificity can be acquired by retroviral transfer of the T-cell receptor to peripheral-blood-derived T lymphocytes. Until now, the application of retroviral transfer of TCRs has mainly been limited to the transfer of HLA class I restricted TCRs. [15][16][17][18][19][20] However, the specificity of HLA class II restricted T lymphocytes can also be transferred to other T c...

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The DBY gene codes for an HLA-DQ5–restricted human male-specific minor histocompatibility antigen involved in graft-versus-host disease

Abstract: Graft rejection or graft-versus-host (GVH)disease

Cited by 145 publications

References 32 publications

Gender-Specific Gene Expression in Post-Mortem Human Brain: Localization to Sex Chromosomes

Gender-Specific Gene Expression in Post-Mortem Human Brain: Localization to Sex Chromosomes

The impact of donor gender on outcome of allogeneic hematopoietic stem cell transplantation for multiple myeloma: reduced relapse risk in female to male transplants

HLA class II restricted T-cell receptor gene transfer generates CD4+ T cells with helper activity as well as cytotoxic capacity

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