The Effect of Hla Matching on Kidney Graft Survival in Separate Posttransplantation Intervals

Thorogood, J.; Gg, Persijn; Gm, Schreuder; D’Amaro, J.; Fa, Zantvoort; Houwelingen, Hans C. van; Jj, van Rood

doi:10.1097/00007890-199007000-00027

Cited by 95 publications

(29 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is well known that some MHC-I mismatches are more clinically important than others (6,7). Thus, interlocus (A vs. B) (34)(35)(36)(37)(38) and intralocus hierarchies of immunogenicity have been described, including HLA-A2 (48,49), HLA-A2 and -A28 (39), HLA-B27 (50,51), HLA-B35 (52) and HLA-B44 (33,(53)(54)(55). However, it has proved difficult to predict which MHC mismatches might be most relevant to allograft survival.…”

Section: Discussionmentioning

confidence: 99%

Immunodominance Hierarchies and Gender Bias in Direct TCD8-Cell Alloreactivity

Mifsud

Purcell

Chen

et al. 2008

American Journal of Transplantation

View full text Add to dashboard Cite

Allogeneic solid organ transplantation often occurs across multiple donor-recipient HLA mismatches with consequent risk of allograft rejection. However, there is growing evidence that not all HLA mismatches are equivalent in their stimulation of allogeneic T cells making it important to determine which of these might be more significant as predictors of allograft rejection. To this end, we used defined antigen-presenting cell (APC) transfectants expressing single MHC-I allotypes as target cells that could discriminate the relative contribution of individual mismatched MHC-I allotypes to direct T-cell alloreactivity. We demonstrate remarkably reproducible patterns of immunodominance in reactivity across mismatched MHC-I allotypes. These patterns are HLA context-dependent, partly reflecting alloantigenic competition in responder cell responses. In strong alloresponses, we also observed an increased percentage of alloreactive T CD8 cells in female responders, regardless of the stimulator gender, highlighting HLA-independent factors in the potency of the alloresponse. This approach provides a potential measure of specific alloreactive T cells that could be used in clinical practice for selection of donors, assessment of posttransplant outcomes, modulation of immunosuppression and detection of rejection episodes.

show abstract

Section: Discussionmentioning

confidence: 99%

Immunodominance Hierarchies and Gender Bias in Direct TCD8-Cell Alloreactivity

Mifsud

Purcell

Chen

et al. 2008

American Journal of Transplantation

View full text Add to dashboard Cite

show abstract

“…showed that IRF-2, a repressor of transcription (13) (54,55). This may be due to locus-specific differences between the class I proteins (17).…”

Section: Discussionmentioning

confidence: 99%

Transcriptional regulation of HLA-A and -B: differential binding of members of the Rel and IRF families of transcription factors.

Girdlestone

Isamat

Gewert

et al. 1993

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

View full text Add to dashboard Cite

HLA-A and -B transplantation antigens can be expressed differentiafly at the basal level and in response to interferons (IFNs). To determine which DNA control elements and nuclear factors are responsible for these differences,HLA-A and -B upstream regulatory regions were used in expression and mobility-shift analyses. The HLA-A enhancer was found to contain two Rel (KBF/NF-#cB) binding motifs, while the HLA-B enhancer has only one and is transactivated less well by overexpression of the NF-#cB p65 subunit. transcription (13, 14). Overexpression of IRF-1 has been shown to increase the basal and IFN-induced levels of class I expression (15, 16).HLA-A and -B genes are highly homologous but exhibit locus-specific differences in both their transcribed (17) andThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.upstream regions (18,19) and are not tightly coordinated in their regulation. They can differ in basal and induced levels of expression, with cortical thymocytes and related thymomas such as MOLT-4, for example, expressing low levels of HLA-A but undetectable , while HLA-B loci respond more strongly to IFNs (21,22) and are subject to stronger suppression by c-myc expression (23). We report here that some of the locus-specific differences between the ENH and IRE of HLA-A and -B have significant effects on the binding of the Rel and IRF families of transcription factors and consequently on the regulation of the two loci. MATERIALS AND METHODSCell Culture, Transfection, and Chloramphenicol Acetyltransferase (CAT) Assays. MOLT4 and YHHH (24) cell lines were maintained in Dulbecco's modified Eagle's medium, and JM and Daudi in RPMI 1640 medium, all with 5% fetal bovine serum. Induction of NF-KB in JM cells was achieved by a 2-hr treatment with phytohemagglutinin (PHA, 5 ,ug/ml; Sigma) and phorbol 12,13-dibutyrate (PBt2, 50 nM; Sigma). Transfections and CAT assays were performed as described (25). Cells were harvested 20 hr after transfection. IFN-aA (kindly provided by M. Brunda, Hoffmann-La Roche) was added after transfection at 2000 units/ml where indicated.Plasmids. CAT reporters were produced by cloning synthetic oligonucleotides into an Sph I site introduced into the Bgl II site at the 5' end of the metallothionein promoter of pMCAT3 (26) and verified by double-stranded sequencing. The Rel p50 and p65 expression plasmids (27) were kindly provided by A. Baldwin (University of North Carolina, Chapel Hill) and the CMV-GalVP16 vector (28) by P. O'Hare (Marie Curie Research Institute, Oxted, Surrey, U.K.).Electrophoretic Mobility-Shift Assays. Nuclear extracts from cell lines were prepared (29) and mobility-shift assays were performed (25) as described. Baculovirus Expression of IRF-1 and IRF-2. Human IRF-1 and IRF-2 clones were obtained from the lymphoid lines HUT78 and MOLT-4, respectively, by two rounds of amplification by polymerase chain reaction...

show abstract

“…Similarly, infection with certain viruses may result in the generalized loss, locus-specific loss, or locus-specific up-regulation of class I glycoproteins (25)(26)(27)(28)(29). Clinical studies indicate that the relative importance of these molecules differs in allograft rejection (30,31). These observations strongly indicate that the regulation of expression of MHC class I genes may determine their functional relevance in a particular physiological context.…”

mentioning

confidence: 99%

The Locus-specific Enhancer Activity of the Class I Major Histocompatibility Complex Interferon-responsive Element Is Associated with a γ-Interferon (IFN)-inducible Factor Distinct from STAT1α, p48, and IFN Regulatory Factor-1

Vallejo

Pease

1996

Journal of Biological Chemistry

View full text Add to dashboard Cite

Recent analyses of the upstream regulatory regions of the class I major histocompatibility complex genes in higher primates provided a generalized structural basis for the differential expression of A-and B-locus gene products in response to specific physiological stimulus. Among the regulatory sequences that differ between the loci is the interferon-responsive element (IRE). While the B-IRE is conserved, the A-IREs have species-specific sequence variation. We previously demonstrated that the B-IRE was an interferon (IFN)-inducible enhancer, whereas none of the A-IREs were functional. In the present study, we examined the biochemical basis for the enhancer activity of the conserved B-IRE and found that this may be attributed to a novel ␥-IFN-inducible factor. This factor accumulated in nuclei of cells within minutes of exposure to ␥-IFN. Its appearance was independent of de novo protein synthesis. However, it was not detected in nuclei of cells treated with herbimycin A, suggesting that its appearance depends on a protein kinase activation pathway. Supershift assays indicated that it was distinct from STAT1␣, IFN regulatory factor-1, and p48, transcription factors known to bind IRElike sequences found in regulatory regions of many nonmajor histocompatibility complex ␥-IFN-responsive genes. Competition assays show that this novel factor bound B-IRE with relatively high affinity, about 100-fold more than that for the A-IRE sequence. This factor was also present in STAT1␣ and p48 somatic mutants that also exhibited B-IRE enhancer activity in reporter gene bioassays in a manner similar to those seen with wild type cells. These observations indicate the existence of a novel ␥-IFN-dependent transcriptional activation pathway that correlates with the differential enhancer activity of the HLA-B IRE.

show abstract

The Effect of Hla Matching on Kidney Graft Survival in Separate Posttransplantation Intervals

Cited by 95 publications

References 0 publications

Immunodominance Hierarchies and Gender Bias in Direct TCD8-Cell Alloreactivity

Immunodominance Hierarchies and Gender Bias in Direct TCD8-Cell Alloreactivity

Transcriptional regulation of HLA-A and -B: differential binding of members of the Rel and IRF families of transcription factors.

The Locus-specific Enhancer Activity of the Class I Major Histocompatibility Complex Interferon-responsive Element Is Associated with a γ-Interferon (IFN)-inducible Factor Distinct from STAT1α, p48, and IFN Regulatory Factor-1

Contact Info

Product

Resources

About