SEARCH · PubMed Health

Results for “Histocompatibility”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 253 records · Page 14Linked to original sources

PubMed1995

Histocompatibility testing for kidney transplantation: an update.

Histocompatibility testing prior to kidney transplantation is an established necessity. Recipient sensitization to HLA specificities affects the efficacy of the lymphocytotoxic cross-match and influences the achievable HLA mismatch. Within Europe most cadaver donor kidneys are allocated on the basis of minimum histocompatibility mismatch contrasting with the North American system which allows for exchange of kidneys only where there is no detectable donor/recipient mismatch. There is also a contrast between the immunosuppression protocols used in these continents with, in general, more aggressive regimens used in North America. In the 1990s there has been considerable refinement in the techniques available to histocompatibility laboratories for definition of HLA phenotypes and genotypes and some obstacles to successful transplantation have been overcome. We review some of these changes with particular reference to our own experience.

Antibodies↗

PubMed1999

Repression of major histocompatibility complex genes by a human trophoblast ribonucleic acid.

The suppression of polymorphic major histocompatibility complex antigen expression in human trophoblasts is critical for the avoidance of a cell-mediated immune response by maternal lymphocytes against cells expressing paternal antigens. In this study, a repressor of major histocompatibility complex gene expression was cloned by negative immunoselection using a trophoblast cDNA expression library in interferon-gamma-responsive human cells. The sequence of this regulatory gene was analyzed, and the functions of the transfected cDNA or microinjected gene product were examined in interferon-gamma-responsive cells by immunocytochemical methods. The repressor, called TSU-- trophoblast STAT (signal transducers and activators of transcription) utron (untranslated region of an mRNA)--reduced STAT1 nuclear translocation and suppressed major histocompatibility complex class II antigen expression at high doses of interferon-gamma and class I expression at low doses of interferon-gamma. TSU encoded a small, untranslated poly-A+-RNA that appeared to bind STAT1 through pairs of motifs analogous to STAT-binding promoter sequences. These promoter-like motifs, but no open reading frame, were conserved in a TSU-related gene in goats. Northern blot analysis demonstrated that TSU was expressed as a 0. 5-kilobase (kb) RNA in placenta and as an ubiquitous 4.4-kb RNA. TSU expression may protect trophoblasts from immune attack and promote the survival of the placenta and fetus.

Base Sequence↗

PubMed1977

Inhibition of the mixed leucocyte reaction by histocompatibility antibodies requires the Fc part.

We have examined the effect in mixed leucocyte culture (MLC) with rat cells of the IgG fraction of alloantibodies against the major histocompatibility complex (anti-BN major) and against some of the minor histocompatibility antigens. Anti-BN major specifically inhibited the MLC response, both when BN cells were responding and stimulating cells. Absorption with BN erythrocytes completely removed the haemagglutinating antibodies but had no effect of MLC inhibition, while absorption with BN lymphocytes removed MLC inhibition as well as haemagglutinating antibodies. The F(ab')2 fragments of anti-BN major did not inhibit MLC, although they still had the capacity to combine specifically with BN lymphocytes. We therefore suggest that the inhibition of MLC responses by alloantibodies is either because of a cytotoxic effect (even if cytotoxicity could not be demonstrated in unmixed cultures) or a blocking of antibody-coated lymphocytes by Fc receptor-bearing cells. Antibodies against minor histocompatibility antigens did not inhibit MLC.

Animals↗

PubMed1980

Genetics of kidney allograft survival in dogs. III. Relevance of histocompatibility matching in immunosuppressed recipients.

The relevance of matching for the serologically defined (SD) and lymphocyte-defined (LD) antigens of the major histocompatibility complex (MHC) for renal allograft survival was evaluated in a dog model. Kidney recipients were treated with a standard regimen of immunosuppressive drugs (azathioprine, 2 mg/kg body wt, and prednisolone, 1 mg/kg body wt, daily i.v.) after transplantation. In seven of the eight SD- and LD-identical beagle littermate donor-recipient pairs (DRPs), and in all seven SD- and LD-identical beagle nonlittermate DRPs, kidney function remained normal for the period of 150 days during which immunosuppressants were given. Of the 8 beagle littermate DRPs differing in one haplotype and all 25 unrelated mismatched mongrel DRPs, kidney function deteriorated during immunosuppressive therapy, and most of the recipients died eventually from graft rejection. Thus, it seems that, in moderately immunosuppressive dogs, non-DLA incompatibilities rarely, if ever, cause rejection, whereas DLA incompatibilities almost always do so. The data differ from those obtained in a previous study in nonimmunosuppressed dogs, in which non-DLA incompatibilities seemed to be as strong as DLA incompatibilities in this respect. Differences in minor histocompatibility antigens can apparently be overcome more easily by immunosuppressive drug therapy than differences in major histocompatibility antigens. After the gradual complete withdrawal of immunosuppression, 11 of the 15 matched littermate and nonlittermate DRPs survived for another 150 days or more, implying that some kind of unresponsiveness was induced in those dogs.

Animals↗

PubMed1981

Implication of the H-2L locus in hybrid histocompatibility (Hh-1).

The Hh-1 (hybrid histocompatibility) effect in which F1 hybrids with heterozygosity at the "D end" of the H-2 complex can reject parental grafts of the H-2b haplotype was examined in four H-2 mutants wherein the mutation had affected the H-2Db, H-2Dd, or H-2Ld genes. In bone marrow grafting experiments it was shown that two separate mutations affecting the H-2Db locus did not affect the Hh-1 gene, suggesting that H-2Db and Hh-1 are probably two different genes. By contrast, experiments with two mutants, one affecting the H-2Dd and H-2Ld loci (B10.D2-H-2dm1) and the other a loss mutation at the H-2Ld locus (BALB/c-H-2dm2), demonstrate an alteration in the hybrid histocompatibility phenomenon and the presumption is made that the Hh-1 and H-2Ld locus are identical. This presumption was supported by studies of Hh-1 using the EL4 tumor grafting model where marked differences in growth were noted in the (B10 X BALB/c)F1 and (B10 X BALB/c-H-2dm2)F1 hybrids. By contrast, the functionally related natural killer (NK) phenomenon appeared to be the same in the BALB/c parent and dm2 mutant. Hybrid histocompatibility is a complex phenomenon but at this time we conclude that the H-2L locus is related to, if not identical to the Hh-1 gene but the H-2L locus is distinct from genes affecting the NK phenomenon.

Animals↗

PubMed1991

Prevention of transfusion-induced sensitization to minor histocompatibility antigens on DLA-identical canine marrow grafts by gamma irradiation of marrow donor blood.

Dogs given total-body irradiation and marrow transplants from DLA-identical littermates exhibit prompt and sustained hematopoietic engraftment. However, animals given three preceding blood transfusions from the marrow donor before transplant become sensitized and reject the marrow graft. Rejection is due to exposure to polymorphic minor non-DLA histocompatibility antigens expressed on blood mononuclear cells. We sought to determine whether heat treatment would prevent blood from sensitizing recipients in this model since heating blood to 45 degrees C for 45 min abrogates the ability of blood mononuclear cells to stimulate in mixed lymphocyte culture. Three of 4 evaluable dogs given heat-treated blood before transplant rejected their marrow grafts. To prevent possible reexpression/reacquisition of mononuclear cell functional activity in vivo after transfusion, subsequent dogs were given heated blood that was additionally exposed to 2000 cGy gamma irradiation. Eight of 10 evaluable dogs given blood treated in this fashion engrafted. Unexpectedly, 9 out of 10 evaluable dogs transfused with blood treated only with gamma irradiation also engrafted. These results demonstrate that treatment of blood with gamma irradiation alone or in combination with heat prevents transfusion-induced sensitization to minor histocompatibility antigens. Results from this canine model suggest that blood products be gamma irradiated before transfusion in patients who are transplant candidates in order to prevent sensitization to minor histocompatibility antigens and reduce the risk of marrow graft rejection.

Animals↗

PubMed1997

Role of non-major histocompatibility complex antigens in the rejection of transplanted myoblasts.

Myoblasts obtained from donors histoincompatible for several non-major histocompatibility complex antigens (i.e., including minor histocompatibility antigens) and from syngeneic donors were transplanted without any immunosuppression into the muscles of male dystrophic C57BL/10J mdx/mdx mice. Myoblasts from syngeneic mice resulted in the formation of a high percentage of dystrophin-positive fibers 16 weeks after the transplantation. There was no evidence of a cellular immune reaction against the donor myoblasts, i.e., no infiltration by CD4 or CD8 lymphocytes and no increased expression of granzyme B and interferon-gamma mRNAs. Transplantation of myoblasts obtained from donors histoincompatible only for non- major histocompatibility complex antigens produced a transient increase of dystrophin-positive fibers at 4 weeks after transplantation for some donor strains but not for others. For donor strains that did produce an increase at 4 weeks, the number of dystrophin-positive fibers was reduced 16 weeks after the transplantation. There was evidence of a cellular immune reaction-infiltration by CD4 and by CD8 lymphocytes and increased expression of granzyme B and interferon-gamma mRNAs. Transplantation of myoblasts obtained from male C57BL/10J +/+ mice into female C57BL/10J mdx/mdx mice also led to the presence of only a few dystrophin-positive fibers with the same signs of cellular immune reaction. In this later case, the cellular immune response was attributed to the H-Y minor antigens. Finally, antibodies against fetal calf serum were detected after both syngeneic and nonsyngeneic transplantations, indicating that the culture medium may also be a source of antigens. In mice, the presence of these antibodies against culture medium did not reduce the success of a first syngeneic transplantation.

Actins↗

PubMed1999

The impact of recurrent glomerulonephritis on graft survival in recipients of human histocompatibility leucocyte antigen-identical living related donor grafts.

BACKGROUND: Graft loss due to rejection is uncommon after human histocompatibility leukocyte antigen-identical living related donor (LRD) transplantation, resulting in an excellent long-term graft survival. Data on the impact of recurrence of the original disease on graft survival after LRD transplantation are scarce. METHODS: We have studied the influence of recurrent glomerulonephritis in adult recipients of a human histocompatibility leukocyte antigen-identical LRD graft transplanted in our center in the period from 1968 to 1996. To that end, the data of 33 patients with proven or suspected primary glomerulonephritis and 27 patients with nonglomerular diseases were analyzed. RESULTS: The patient survival was similar in both groups at 5, 10, and 20 years. The functional graft survival, i.e., graft survival after censoring for death, was, however, significantly worse for patients with glomerulonephritis as underlying disease (P<0.01). At 5 years graft survival was 100% vs. 88%, at 10 years 100% vs. 70%, and at 20 years 100% vs. 63%, respectively. Thus none of the patients with nonglomerular diseases lost a graft, whereas eight grafts were lost in the group of patients with glomerulonephritis. The main cause of graft loss in this patient group was recurrent glomerulonephritis (n=5), whereas chronic vascular rejection caused graft loss in two patients and occlusion of a transplant artery was the cause in one. A clinically significant proteinuria was detected in six more patients in the glomerulonephritis group: a recurrent glomerulonephritis was diagnosed in four patients and in two patients there was no biopsy. The cumulative incidence of recurrence was as high as 45% at 12 years after transplantation. CONCLUSION: Recipients of a human histocompatibility leukocyte antigen-identical LRD kidney have a good prognosis with respect to graft survival. After censoring for death, recurrent glomerulonephritis is the main cause of graft failure in these patients and the impact of recurrent disease on graft survival will become even more prominent with longer follow-up.

Adult↗

PubMed1999

Recognition of major histocompatibility complex class II antigens by two anti-HLA-DR monoclonal antibodies on canine marrow cells correlates with effects on in vitro and in vivo hematopoiesis.

BACKGROUND: The role of major histocompatibility complex class II antigens in hematopoiesis is not well defined. We have shown that in vitro depletion of HLA-DR+ cells from canine marrow (e.g., by anti-HLA-DR monoclonal antibody [mAb] H81.9 and complement) prevents hematopoietic recovery. In vivo administration of the same mAb H81.9 after transplantation of unmanipulated autologous marrow results in graft failure. In vitro mAb H81.9 inhibited colony formation from short-term and long-term marrow cultures. METHODS AND RESULTS: We investigated the effect of another mAb, Ca1.41, which also recognizes nonpolymorphic determinants on human (HLA-DR) and canine major histocompatibility complex class II antigens but is reactive with a narrower spectrum of cells in both canine peripheral blood and marrow than mAb H81.9 (and other anti-HLA-DR mAbs). In contrast to all other anti-HLA-DR mAbs tested, Ca1.41 did not interfere with colony formation in short-term or long-term marrow cultures and spared a population of small mononuclear cells with low forward light scatter that was eliminated via apoptosis by exposure to mAb H81.9. These target cells included lymphocytes and CD34+ hemopoietic precursors that expressed MHC class II molecules as determined by mAb H81.9 but not by mAb Ca1.41. In addition, transmembrane signaling and up-regulation of interleukin-1beta mRNA occurred with mAb H81.9 but not with Ca1.41. Transplantation of autologous marrow treated in vitro cytolytically with mAb Ca1.41 allowed for complete hematopoietic reconstitution. Further, in vivo administration of Ca1.41 posttransplant did not lead to autologous graft failure as had been observed with mAb H81.9. CONCLUSIONS: These results support the notion that major histocompatibility complex class II is expressed on early hematopoietic precursor cells but recognition is dependent upon the mAb used. Preliminary studies show that mAb H81.9 triggered transmembrane signaling, resulting in up-regulation of interleukin-1beta and apoptosis, although mAb Ca1.41 did not. The fact that Ca1.41 binding was modified in the presence of exogenous invariant chain-derived peptide suggests that both binding and signaling are peptide dependent.

Animals↗

PubMed2000

Human cytomegalovirus blocks interferon-gamma stimulated up-regulation of major histocompatibility complex class I expression and the class I antigen processing machinery.

Interferon-gamma stimulates major histocompatibility complex (MHC) class I antigen processing and presentation by inducing the expression of major histocompatibility complex class I heavy chains, beta2-microglobulin, the transporter associated with antigen processing, and components of the proteasome complex. We demonstrate that this effect of interferon-gamma on the major histocompatibility complex class I pathway is inhibited in human cytomegalovirus-infected fibroblasts and endothelial cells. This is the result of a direct human cytomegalovirus/cell interaction leading to a block in interferon-gamma signal transduction beginning at early times after infection and peaking at 72 hr after infection. These observations suggest a novel level of herpesvirus interference with antigen processing: protection of infected cells from the immunoregulatory effects of interferon-gamma. Thus protected, human cytomegalovirus persists and may exacerbate graft rejection or lead to fulminant infection in the immunocompromised transplant recipient.

Antigen Presentation↗

PubMed1985

Regulation of delayed type hypersensitivity to host histocompatibility antigens during graft-versus-host reactions.

During GvH reactions in irradiated mice a variety of specific anti-host immune responses may occur. One of these is the occurrence of DTH to the host histocompatibility antigens, which may account for the inflammatory aspects of GvH. During acute as well as delayed GvH reactions the occurrence of anti-host DTH precedes the clinical symptoms of GvH disease. The anti-host DTH is mediated by long-lived, recirculating Lyt-1 + 2- T cells that need to proliferate in the irradiated recipients in order to display maximum activity. Not all host histocompatibility antigens can elicit anti-host DTH. H-2I and Mls-locus coded alloantigens do, but H-2K/D coded alloantigens and non-H-2 alloantigens other than Mls-locus coded alloantigens do not. This correlates with the ability to elicit proliferative mixed lymphocyte reactions in vitro but is in contrast to the response of nonirradiated mice to sc administered alloantigens. Under the latter conditions, all histocompatibility antigens induce a state of antigen-specific DTH. While the anti-host DTH is mediated by long-lived, recirculating Lyt-1 + 2- T cells, their response can be amplified by short-lived, sessile Lyt-1 + 2 + T cells. The latter T cell subset reacts to the host H-2K/D alloantigens and/or to non-H-2 alloantigens other than Mls-locus coded products. These cells alone cannot mount an anti-host DTH response. The anti-host DTH can be mitigated by Ts cells and non-T suppressor cells. Appropriate Ts cells can be readily induced by iv preimmunization of the donors with 5 X 10(7) irradiated, recipient-type spleen cells. Non-T suppressor cells can be induced by iv injection of bacterial LPS and simultaneous sc injection of 1 X 10(7) recipient type spleen cells. The suppression induced by these protocols shares several characteristics. In both cases the suppression is long-lasting, i.e., lasts at least 50 d, is transferable to syngeneic mice by spleen and lymph node cells, and both suppressive systems affect the induction of anti-host DTH as well as already activated anti-host DTH reactive T cells. Furthermore, while Ts cells and non-T suppressor cells are specific with regard to their antigen recognition, they are both able to suppress the DTH to a completely different set of host alloantigens. This, however, only occurs if the latter are inherited by the irradiated recipients as bystanders to the type of alloantigens that had activated the suppressor cells in the lymphoid cell donors.

Animals↗

PubMed2006

SiPep: a system for the prediction of tissue-specific minor histocompatibility antigens.

Approximately 50 years ago it was found that inbred strains of mice were able to reject tumours and skin grafts from major histocompatibility complex (MHC) identical donors. They proposed that additional transplantation antigens must exist outside the MHC. These were described as minor histocompatibility antigens (mHAgs). Since then, related studies in humans have identified 16 human mHAgs. The aim of this work is to increase the number of known mHAgs by prediction of candidate minor histocompatibility loci by identifying coding single nucleotide polymorphisms (SNPs) where the amino acid variation lies within an MHC-binding peptide and alters the ability of that peptide to bind. We have developed an algorithm called SiPep which uses peptide sequences derived from the flanking regions of known non-synonymous SNPs, various MHC-binding and proteolytic cleavage evaluation methods and protein expression data to predict mHAgs. We have processed 45094 SNPs using the SiPep algorithm and have stored the results in a database called SNPBinder. The facilities to process submitted proteins through the SiPep algorithm as well as the SNPBinder database are available to the public. A set of peptides that are predicted as possible mHAgs by the SiPep algorithm have been tested using refolding assays and gel filtration and the results are presented in this paper. The SiPep tools and SNPBinder database are available free of charge via the internet. An HTML interface providing search facilities can be found at the following address: http://www.sipep.org/.

Algorithms↗

PubMed1974

Antireceptor antiserum causes specific inhibition of reactivity to rat histocompatibility antigens.

The antigen receptor of lymphocytes destined to form antibody appears to have the characteristics of the immunoglobulin produced. Antibody directed against the combining region of this immunoglobulin should interact with the combining region of the cell receptor for the antigen. Purified Lewis rat alloantibody prepared against Brown Norway (BN) rat histocompatibility antigens was used to immunize L x BN F(1) hybrids. The resultant antiserum has anti-receptor activity because (i) it yields precipitin lines in gel diffusion when reacted against the immunizing alloantibody; (ii) it inhibits the hemagglutinin antibody response of Lewis rats to BN histocompatibility antigens; and (iii) it inhibits the local graft-versus-host response of Lewis lymphoid cells against BN antigens. This suggests that antireceptor antibody may inhibit cell-mediated responses as well as antibody responses to histocompatibility antigens and may play a role in the regulation of immune responses to such antigens.

Animals↗

PubMed1987

Anti-influenza virus cytotoxic T lymphocytes recognize the three viral polymerases and a nonstructural protein: responsiveness to individual viral antigens is major histocompatibility complex controlled.

It has recently been shown that antiviral major histocompatibility complex class I-restricted cytotoxic T lymphocytes can recognize proteins that serve as internal viral structural components (influenza A virus nucleoprotein, vesicular stomatitis virus nucleocapsid protein). To further examine the role of internal viral proteins in cytotoxic T-lymphocyte recognition, we constructed recombinant vaccinia viruses containing individual influenza A virus genes encoding three viral polymerases (PB1, PB2, PA) and a protein not incorporated into virions (NS1). We found that cells infected with each of these recombinant vaccinia viruses could be lysed by anti-influenza cytotoxic T lymphocytes. Cytotoxic T-lymphocyte responsiveness to the individual viral antigens varied greatly between mouse strains. By using congenic mouse strains, responsiveness to PB1 and PB2 was found to cosegregate with major histocompatibility complex haplotype. These findings provide further evidence that internal antigens play a critical role in cytotoxic T-lymphocyte recognition of virus-infected cells. Additionally, they suggest that the cytotoxic T-lymphocyte response to viral antigens may often be restricted to only a fraction of the major histocompatibility complex class I repertoire.

Animals↗

PubMed1989

Class I major histocompatibility proteins as cell surface receptors for simian virus 40.

Class I major histocompatibility complex proteins appear to be the major cell surface receptors for simian virus 40 (SV40), as implied by the following observations. Adsorption of SV40 to LLC-MK2 rhesus monkey kidney cells specifically inhibited binding of a monoclonal antibody (MAb) against class I human lymphocyte antigen (HLA) proteins. Conversely, pretreatment of LLC-MK2 cells with anti-HLA MAbs inhibited infection by SV40. The ability of anti-HLA to inhibit infection was greatly reduced when the order of addition of the anti-HLA and the virus was reversed. Infection was also inhibited by preincubating SV40 with purified soluble class I protein. Finally, human lymphoblastoid cells of the Daudi line, which do not express class I major histocompatibility complex proteins, were infected at relatively low levels with SV40 virions. In a control experiment, we found that pretreatment of cells with a MAb specific for the leukocytic-function-associated antigen LFA-3 actually enhanced infection. This finding may also support the premise that class I major histocompatibility complex proteins are receptors for SV40.

Antibodies, Monoclonal↗

PubMed1983

Differential expression of porcine major histocompatibility DNA sequences introduced into mouse L cells.

The expression of a porcine genomic DNA segment containing a major histocompatibility gene and its chromatin structure in mouse L cells have been investigated. The transformed cells, which contain about two copies of the 17.8-kilobase pig DNA insert per haploid genome, stably and uniformly express major histocompatibility antigen on their surfaces. This expression is the result of differential transcription of the 3-kilobase major histocompatibility gene; the other 14 kilobases of pig sequences flanking the coding sequence are not transcribed. Although the entire pig DNA segment is packaged into nucleosomes, only the transcriptionally active DNA sequences are packaged in a DNase I-sensitive conformation. These results suggest that the expression of this foreign DNA is actively regulated in L cells.

Animals↗

PubMed1988

Microrecombinations generate sequence diversity in the murine major histocompatibility complex: analysis of the Kbm3, Kbm4, Kbm10, and Kbm11 mutants.

The mechanism that generates spontaneous mutants of the Kb histocompatibility gene was analyzed. Nucleotide sequence analysis of four mutant genes (Kbm3, Kbm4, Kbm10, and Kbm11) revealed that each mutant K gene contains clustered, multiple nucleotide substitutions. Hybridization analyses of parental B6 genomic DNA and cloned class I genes with mutant-specific oligonucleotide probes, followed by sequence analyses, have identified major histocompatibility complex class I genes in the K, D, and Tla regions (K1, Db, and T5, respectively) that contain the exact sequences as substituted into mutant Kb genes. These data provide evidence for the hypothesis that the mutant Kb genes are generated by a microrecombination (gene conversion) mechanism that results in the transfer of small DNA segments from class I genes of all four regions of the major histocompatibility complex (K, D, Qa, and Tla) to Kb. Many of the nucleotides substituted into the mutant Kb genes were identical to those found in other naturally occurring K alleles such as Kd. Thus, we propose that the accumulation of microrecombination products within the K genes of a mouse population is responsible for the high sequence diversity among H-2 alleles.

Alleles↗

PubMed1986

Pituitary transplantation: cyclosporine enables transplantation across a minor histocompatibility barrier.

Pituitary glands from neonatal donors were transplanted to the median eminence of hypophysectomized adult rats. Rats with transplants were then treated for 2 weeks with the immunosuppressive drug cyclosporine. For 5 weeks thereafter, blood was drawn at regular intervals for determination of serum thyroxine, prolactin, and luteinizing hormone. Cyclosporine-treated recipients of grafts with minor histocompatibility differences had normal levels of thyroxine and prolactin, whereas untreated animals did not. In addition, the treated animals responded to oophorectomy with a marked elevation in serum luteinizing hormone. This evidence indicates that cyclosporine enables successful transplantation across a minor histocompatibility barrier. It also suggests that these grafts interact with the hypothalamus. Transplantation across a major histocompatibility barrier was unsuccessful even in the presence of cyclosporine.

Animals↗