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At least 199 records · Page 11Linked to original sources
PubMed1972

Third party mixed-leukocyte culture test: a potential new method of histocompatibility testing.

The disparity index is an expression of histocompatibility difference between two siblings with identical human leukocyte antigen (HL-A) type who are nonreactive in mixed leukocyte culture (MLC) test. This index is derived from a third-party MLC test. The disparity index was found to be correlated with the severity of graft-versus-host reaction in bone marrow transplantation between HL-A-identical siblings. The disparity index may prove to be a useful means of predicting the severity of graft-versus-host reaction and the outcome of bone marrow graft when HL-A- and MLC-matched sibling donors are studied. The third-party MLC test is offered as a new method of histocompatibility testing. It may provide a useful model for the study of immunogenetics relative to so-called weaker histocompatibility determinants in man and experimental animals.

Antigens↗
PubMed1997

A complex major histocompatibility complex D locus variant generated by an unusual recombination mechanism in mice.

A spontaneous variant of the mouse class I major histocompatibility complex D(b) gene, designated D(bm28), is characterized. This mutation consists of a cluster of nucleotide substitutions in exon 3 that resembles the product of a classical gene conversion event in that the substituted nucleotides appear to be templated. However, D(bm28) is distinctive, because no single donor gene containing the nucleotide sequence of the mutation exists in the genome of the parent strain. The mutation is consistent with the expected result of an interaction of two donor genes at the target locus during a single recombination event. While no known genetic mechanism gives rise to this class of mutation, we have established that 10 percent of spontaneous class I mutations in the mouse major histocompatibility complex have this complex phenotype. This process occurs at the D locus and the K locus. The significance of this kind of genetic interaction may extend beyond the major histocompatibility complex and have importance in shaping other multigene families.

Animals↗
PubMed1972

Histocompatibility-linked immune response gene function in guinea pigs. Specific inhibition of antigen-induced lymphocyte proliferation by alloantisera.

A number of autosomal dominant immune response (IR) genes have been identified in both mice and guinea pigs. These IR genes have been shown to be linked to the major histocompatibility antigens of the species and to be functionally expressed primarily in T lymphocytes. In order to more fully understand the relationship between IR genes, histocompatibility antigens, and immune recognition, the effect of specific alloantisera on lymphocyte stimulation induced by antigens under control of IR genes was examined. Using lymphocytes from strain 2 or strain 13 animals, the in vitro proliferative responses both to antigens which are known to be under genetic control (DNP-GL in strain 2 guinea pigs and GT in strain 13 guinea pigs) and to an antigen which is not known to be under genetic control (PPD) were inhibited to a similar degree and to a much greater extent than the response to phytohemagglutinin. However, when cells from F(1) (2 x 13) animals are used, the alloantisera markedly inhibit only the response which is linked to the histocompatibility antigens against which the serum is directed. Thus, the anti-2 serum inhibited the response to DNP-GL but not to GT; the anti-13 serum inhibited the response to GT but did not affect DNP-GL response. The inhibitory activity of the alloantisera could not be removed by absorption with gamma globulin of the opposite strain. It can be concluded from these observations that immune response genes produce a cell surface-associated product and that this product plays a role in the mechanism of antigen recognition by the T lymphocyte. The mechanisms by which alloantisera block this process of antigenic recognition is not resolved nor is the relationship between the IR gene product and the antigen-binding receptor of the T lymphocyte. The approach described here offers a powerful tool for the resolution of these problems.

Animals↗
PubMed1978

Analysis of the major histocompatibility complex in Syrian hamsters. II. Linkage studies.

The genetic control of the histocompatibility antigens that induce strong alloreactions in Syrian hamsters was examined. Genetic studies revealed that the alloantigens involved in skin graft rejection, graft-versus-host reactions, and mixed lymphocyte reactions are under dominant single gene control and that these genetic loci are closely linked. These data suggest that this strong histocompatibility locus (i) may represent the major histocompatibility complex equivalent in this species, and this locus or group of loci has been called Hm-1. In addition, studies concerning the genetic control of the immune response to bovine serum albumin suggest that the high response is under dominant, single gene control; however, this gene is not linked to Hm-1.

Animals↗
PubMed1985

Synergism between minor and major histocompatibility antigens in the rejection of cultured allografts.

Thyroid lobes cultured in hyperbaric oxygen were transplanted into recipients that differed from the donor in major histocompatibility complex (MHC) antigens alone (2 strain combinations), minor histocompatibility antigens alone (5 strain combinations), or both (5 strain combinations). Significant foci of lymphocytic infiltration, referred to here as a delayed type hypersensitivity reaction, were seen only if there were minor antigenic differences, and a significant number of rejections occurred only if there were both minor plus MHC antigenic differences. Thus, these results demonstrated a synergism between some minor and MHC histocompatibility antigens in the rejection of cultured allografts. Possible mechanisms of this synergism are discussed.

Animals↗
PubMed1994

Gamma-irradiation of pretransplant blood transfusions from unrelated donors prevents sensitization to minor histocompatibility antigens on dog leukocyte antigen-identical canine marrow grafts.

Pretransplant blood transfusions from a dog leukocyte antigen (DLA)-identical canine littermate marrow donor will sensitize the recipient to non-DLA-linked polymorphic minor histocompatibility antigens, which uniformly results in graft rejection. We observed previously that 2000 cGy gamma-irradiation of marrow donor blood transfusions prevented this sensitization and subsequent marrow graft rejection. The purpose of the present study was to determine whether treatment of unrelated blood transfusions with gamma-irradiation would also prevent sensitization. Conceivably, sensitization to minor histocompatibility antigens might be more efficient or potent and thus more difficult to prevent when those antigens are seen in the context of disparity for DLA antigens. Furthermore, this model, in which sensitization to DLA-identical littermate marrow is caused by unrelated blood transfusions, is directly relevant to the clinical circumstances of human marrow transplantation. We assessed sensitization caused by unrelated blood transfusions by monitoring graft outcome in recipients transplanted with DLA-identical littermate marrow after conditioning with 920 cGy total body irradiation. Two thousand cGy gamma-irradiation of unrelated blood transfusions significantly reduced the incidence of transfusion-induced sensitization of recipients. There was successful marrow engraftment in 15 of 16 (94%, P < 0.003) of these animals in contrast to the previous study in which only 7 of 16 (44%) animals engrafted after they were transfused with unmodified blood on the same schedule. These results suggest that blood transfusions for use in humans, especially for patients with aplastic anemia, should be gamma-irradiated in order to reduce the incidence of marrow graft rejection caused by sensitization to minor histocompatibility antigens.

Animals↗
PubMed1996

Immunomodulatory function of major histocompatibility complex-derived peptides.

Recent advances with regard to the structure and function of the major histocompatibility molecules have given rise to a better understanding of T cell receptor interaction with the major histocompatibility complex plus peptide complex on the surface of antigen-presenting cells, and have highlighted the pivotal role of the peptide in determining the subsequent T cell response. There has therefore been increased interest in the use of synthetic peptides to alter T cell responses to foreign antigens. The purpose of this review is to highlight the recent studies which demonstrate the potential immunomodulatory functions of peptides derived from major histocompatibility complex molecules.

Animals↗
PubMed2007

Duffy and Kidd blood group antigens: minor histocompatibility antigens involved in renal allograft rejection?

BACKGROUND: Minor histocompatibility antigens have been poorly defined. Whether Duffy (FY) and Kidd (JK), polymorphic and immunogenic blood group antigens, widely distributed in human organs, expressed and functional in the kidney, could function as minor histocompatibility antigens and be implicated in renal allograft rejection was questioned. STUDY DESIGN AND METHODS: A retrospective, homogeneous, single-center cohort of 370 renal transplants was analyzed. In all donor/recipient pairs, FY and JK polymorphisms were identified by real-time polymerase chain reaction. In all donor/recipient pairs the matching (m) or mismatching (mm) status was defined for both systems. All biopsies were reviewed, and historical screening results for FY and JK alloantibodies and graft survival were retrospectively analyzed. RESULTS: Although graft survival was not different between the groups, it was observed that FY mm grafts had significantly more chronic lesions compared to FY m grafts. HLA-DR11 was more frequent in both recipients (p = 0.0081) and donors (p = 0.0104) of FY mm couples without chronic allograft nephropathy, suggesting a protective effect for this molecule. JK mm grafts had more interstitial inflammation than JK m grafts (p = 0.0369). CONCLUSION: This renal model unmasks for the first time the role of FY and-to a lesser extent-JK antigens as minor histocompatibility antigens and suggests their potential role for other clinical transplant settings.

Adolescent↗
PubMed1985

Histocompatibility antigens on murine tumors.

Recent advances in tumor immunology suggest that the expression of the histocompatibility antigens, encoded by the major histocompatibility complex, is important in controlling the metastatic growth of certain murine tumors. The anomalous expression of histocompatibility antigens in many neoplasms appears to be associated with the ability of these cells to evade the immune system and progress to metastasis. This review examines some of the underlying molecular and immunobiological interactions that might determine the metastatic outcome of cellular transformation.

AKR murine leukemia virus↗
PubMed2003

Major histocompatibility lineages and immune gene function in teleost fishes: the road not taken.

It has become increasingly clear over the course of the past decade that the immune system genes of teleosts and tetrapods are plainly derived from common ancestral genes. The last 5 years, however, have also made it abundantly clear that in the teleost genome some of these genes are organized in a manner very different from that seen in mammals. These differences are probably the result of differences in life history traits, such as fecundancy, within each group of species when faced with an evolutionary fork in the road shortly after their divergence from each other. One group, the tetrapods, including mammals, chose a highly organized linked major histocompatibility complex, while in teleosts the major histocompatibility genes remained unlinked. In this review we will discuss the structural and functional implications of this different organization, particularly for major histocompatibility genes, but drawing on the current knowledge of some other genes for further support for the hypothesis that each group took a different road, one more traveled and one less taken.

Alleles↗
PubMed1976

The major histocompatibility complex and its relationship to allergic disease.

Two tests, the mixed leukocyte culture (MLC) and cell-mediated lympholysis (CML) tests, have been used as in vitro models of the in vivo allograft reaction. These tests have been applied to histocompatibility testing for transplantation as well as to assay of immune function. They involve the use of peripheral blood lymphocytes as "responding" cells in mixed leukocyte culture or as "stimulating" cells in the generation of a proliferative or a cytotoxic response. The proliferative events in MLC are primarily in response to LD antigens of the major histocompatibility complex; the cytotoxic cells use as their targets the SD antigens of that complex. A new method for defining the LD antigens, the primed LD typing (PLT) test, is based on in vitro sensitization of lymphocytes to certain LD antigens of the major histocompatibility complex and their subsequent restimulation with test cells.

ABO Blood-Group System↗
PubMed2005

Matched control study of efficacy of lymphocyte immunotherapy in donor oocyte recipients to support or refute the concept of need for histocompatibility antigen sharing of the couple for benefits.

PURPOSE: To determine if lymphocyte immunotherapy (LIT) improves outcome in recalcitrant donor oocyte recipients. If LIT was found to be similarly effective in this group, the theory of shared maternal/paternal histocompatibility antigens would seem less plausible because the donor oocyte introduces another group of histocompatibility antigens. METHODS: Donor oocyte recipients with a history of failure to conceive despite at least two previous ETs using donor oocytes were given the option of having LIT. They were matched with the very next recipient who declined LIT therapy. Lymphocyte immunotherapy using the male partner's lymphocytes was given two weeks before transfer and twice more if pregnant. RESULTS: Only three controls delivered versus recipients treated with LIT. CONCLUSIONS: The fact that benefit from LIT extended to oocyte recipients challenges the concept that lymphocyte immunotherapy is most beneficial for couples sharing histocompatibility antigens.

Case-Control Studies↗
PubMed1989

Expression of major histocompatibility complex on human medulloblastoma cells with neuronal differentiation.

Medulloblastomas are among the most common malignant brain tumors in children. These tumors consist of immature bipotential cells that may differentiate into neuronal and glial cells. We have established two cell lines for human medulloblastoma. One was derived from a 2-year-old girl with a cerebellar tumor (designated as ONS-76) and another from a 9-year-old girl with a metastatic tumor in the right frontal lobe (ONS-81). The in vitro population-doubling times were 18.6 and 19.2 h, respectively. Immunohistochemical studies showed that both cells possessed neurofilament protein (Mr 145,000 and 200,000) and neuron-specific enolase, without glial fibrillary acidic protein or S-100 protein. Human gamma-interferon enhanced class I major histocompatibility complex antigens on these medulloblastoma cells. Class II major histocompatibility complex antigens were also induced by human interferon-gamma. We here report for the first time the expression of class II major histocompatibility antigens, which play an important role in immune response, on human medulloblastoma cells with neuronal differentiation.

Cell Differentiation↗
PubMed1984

Primary in vitro generation of cytotoxic cells specific for human minor histocompatibility antigens between HLA-identical siblings.

A limiting dilution culture system was developed for the primary in vitro detection of human minor histocompatibility antigens by cytotoxic T lymphocytes (CTL). CTL were generated in primary in vitro culture between two HLA-identical sibling pairs and propagated as stable CTL lines. Population and family studies indicate that these CTL lines recognize minor histocompatibility antigens in an HLA-restricted manner. The antigen recognized by one CTL line is detected on six (out of 37) HLA-B7-positive donors but not on 32 HLA-B7-negative donors. The cytotoxicity of this CTL line is mediated by T3+, T8+ effector cells. The antigen detected by this CTL population is different from all known human minor histocompatibility antigens. The data of this study, like those in the mouse system, suggest that a suppressor cell is diluted out in a limiting dilution culture, which allows the activation of the CTL precursors.

Cytotoxicity Tests, Immunologic↗
PubMed1982

T-cell responses to minor histocompatibility antigens.

We have investigated the helper and cytotoxic T-cell response to minor histocompatibility antigens and generated long term antigen-specific cell lines to them. Antigen-specific activity was selected for by regular restimulation with irradiated cells bearing the antigens in the presence of interleukin 2, so that alloreactivity to other cell surface antigens was gradually lost. Helper T cells cultured over several months were active in vivo and in vitro, but the culturing method eventually selected for cytotoxic T cells at the expense of helper T cells, with concomitant changes in the proportions of cells expressing the Lyt phenotypes. Individual long term cultures of cytotoxic T cells specific for minor histocompatibility antigens were restricted by either H2K or D but not both. Helper T cells to minor histocompatibility antigens derived directly from primed F1 mice did not show restriction to the priming parental haplotype. This is consistent with antigen reprocessing by the F1 antigen presenting cells such that populations of helper T cells restricted by both parental H-2 haplotypes were primed. F1 cytotoxic T cells were restricted to the parental H-2 haplotype used for in vitro boosting, irrespective of which H-2 was used for in vivo priming.

Animals↗
PubMedDate not supplied

Studies of histocompatibility and immune response of chickens selected for resistance and susceptibility to Marek's disease.

Two sets (four lines) of chickens, lines 7 and 6 and lines P and N, the former of each set susceptible and the latter resistant to Marek's disease, were examined for their relative histocompatibility and immunocompetence. Results from the in vivo graft-versus-host response splenomegaly assay, and graft-versus-host chorioallantoic membrane pock formation assay confirmed the within-line, B-locus homozygosity of chickens of lines 7, 6, and N and the heterozygosity of line-P chickens. These assays further confirmed that line-7 and line-6 chickens share identical alleles at the major histocompatibility locus. The capacity of the lines of chickens to elicit specific cell-mediated immune lysis as measured by the release of chromium 51 generally agreed with the in vivo graft-versus-host responses. These data demonstrate that the 51Cr-release assay is a reliable measure of histocompatibility within the avian system.

Animals↗
PubMed1994

Prevention of graft-versus-host disease by peptides binding to class II major histocompatibility complex molecules.

Graft-versus-host disease across minor histocompatibility barriers was induced in two different models by transplanting allogeneic bone marrow and spleen cells into irradiated H-2-compatible recipient mice. In this report, we show that administration of peptides with high binding affinity for the respective class II major histocompatibility complex molecules after transplantation is capable of preventing the development of graft-versus-host disease in two different murine models. The peptides used were myelin basic protein residues 1 through 11 with alanine at position 4 (Ac 1-11[4A]) for I-Au (A alpha uA beta u), and the antigenic core sequence 323 through 339 of ovalbumin with lysine and methionine extension (KM core) for I-As (A alpha sA beta s). In both systems, the mechanism of prevention was found to be major histocompatibility complex-associated, because nonbinding control peptides did not have any effect. Engraftment of allogeneic bone marrow cells was shown by polymerase chain reaction analysis of DNA polymorphisms in a microsatellite region within the murine interleukin-5 gene.

Amino Acid Sequence↗
PubMed1995

A nonlethal conditioning approach to achieve durable multilineage mixed chimerism and tolerance across major, minor, and hematopoietic histocompatibility barriers.

Reconstitution of lethally irradiated mice with a mixture of syngeneic and allogeneic (A+B-->A) bone marrow results in multilineage mixed allogeneic chimerism, donor-specific transplantation tolerance, superior immunocompetence and resistance to graft-vs-host disease. However, the morbidity and mortality associated with lethal irradiation would be a major limitation to the clinical application of chimerism to induce tolerance for solid organ grafts or treat other nonmalignant hematologic diseases. We report here that durable multilineage mixed allogeneic chimerism and donor-specific transplantation tolerance for skin and primarily vascularized allografts can be achieved across multiple histocompatibility barriers using a nonmyeloablative radiation-based approach. The percentage of B10 mouse recipients that engrafted directly correlated with the degree of disparity between donor and recipient and the dose of total body irradiation administered. Although the occurrence of engraftment following conditioning with doses of total body irradiation of > or = 600 cGy was similar for animals receiving bone marrow disparate at MHC or MHC, minor and hematopoietic (Hh-1) loci (67% vs 78%), the level of donor chimerism was significantly less when multiple histocompatibility barriers were present (94.6 +/- 3.8% vs 37.5 +/- 12.5%). Treatment of the recipient with cyclophosphamide 2 days following allogeneic bone marrow transplantation reduced the dose of radiation sufficient for reliable engraftment to only 500 cGy of total body irradiation, regardless of MHC and Hh-1 disparity. Donor chimerism was stable and present in all lineages, with production of lymphoid (T and B cell), NK, and myeloid (erythrocyte, platelet, granulocyte, and macrophage) cells. Mixed chimeras exhibited donor-specific tolerance in vitro, as assessed by mixed lymphocyte culture (MLR) and cytotoxicity (CML) assays, and in vivo to skin and primarily vascularized cardiac allografts. The observation that engraftment and tolerance can be achieved across multiple histocompatibility barriers using nonmyeloablative recipient conditioning may allow allogeneic bone marrow transplantation to be applied to nonmalignant disease states in which lethal conditioning cannot be justified, including the induction of donor-specific tolerance for solid organ transplantation and the treatment of hemoglobinopathies and enzyme deficiency states.

Animals↗