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At least 145 records · Page 8Linked to original sources
PubMed1997

Neuronal expression of class II major histocompatibility complex (HLA-DR) in 2 cases of Pick disease.

BACKGROUND: Pick disease is a progressive form of dementia characterized by personality changes, speech disturbances, inattentiveness, and occasionally extrapyramidal phenomena. Although several variants have been recognized, the pathological profile of Pick disease includes focal frontotemporal atrophy, neuronal loss, astrocytosis, Pick bodies, and Pick cells. To date, little is known about the etiology of Pick disease. OBJECTIVE: To evaluate the possibility of inflammatory processes occurring in Pick disease pathophysiology. DESIGN: Immunohistochemistry for HLA-DR and related molecules was performed in brain tissue from individuals with Pick disease, Alzheimer disease, and diffuse Lewy body disease, as well as from neurologically normal controls. RESULTS: We report the unusual expression of the class II major histocompatibility complex protein Ia (HLA-DR) on neurons in 2 cases of Pick disease. In addition, both cases exhibited a dramatic microglial response. Neuronal HLA-DR immunostaining was not observed in 12 other cases of Pick disease or cases of Alzheimer disease, cases of diffuse Lewy body disease, or in control cases run con-currently. In addition, the pattern of HLA-DR staining observed in Pick disease was confirmed with another monoclonal antibody to HLA-DR. Frequent in vitro inducers of HLA-DR expression and enhanced class I major histocompatibility expression, interferon gamma, and tumor necrosis factor alpha were not detected. CD4-positive T lymphocytes were also not present and class I major histocompatibility complex expression was not detected on neurons or glia from brain tissue with Pick disease. CONCLUSIONS: These results are the first to demonstrate class II major histocompatibility complex expression on neurons. Based on these preliminary results, we suggest that some cases of Pick disease may be complicated by or involve in inflammatory process.

Aged↗
PubMed1999

Cell adhesion and histocompatibility in sponges.

Sponges are the lowest extant metazoan phylum and for about a century they have been used as a model system to study cell adhesion. There are three classes of molecules in the extracellular matrix of vertebrates: collagens, proteoglycans, and adhesive glycoproteins, all of them have been identified in sponges. Species-specific cell recognition in sponges is mediated by supramolecular proteoglycan-like complexes termed aggregation factors, still to be identified in higher animals. Polyvalent glycosaminoglycan interactions are involved in the species-specificity, representing one of the few known examples of a regulatory role for carbohydrates. Aggregation factors mediate cell adhesion via a bifunctional activity that combines a calcium-dependent self-interaction of aggregation factor molecules plus a calcium-independent heterophilic interaction with cell surface receptors. Important cases of cell adhesion are the phenomena involved in histocompatibility reactions. A long-standing prediction has been that the evolutionary ancestors of histocompatibility systems might be found among primitive cell-cell interaction molecules. A surprising characteristic of sponges, considering their low phylogenetic position, is that they possess an exquisitely sophisticated histocompatibility system. Any grafting between two different sponge individuals (allograft) is almost invariably incompatible in the many species investigated, exhibiting a variety of transitive qualitatively and quantitatively different responses, which can only be explained by the existence of a highly polymorphic gene system. Individual variability of protein and glycan components in the aggregation factor of the red beard sponge, Microciona prolifera, matches the elevated sponge alloincompatibility, suggesting an involvement of the cell adhesion system in sponge allogeneic reactions and, therefore, an evolutionary relationship between cell adhesion and histocompatibility systems.

Animals↗
PubMed1997

Histocompatibility gene mutation rates in the mouse: a 25-year review.

Mutation rates of H2 and non-H2 histocompatibility genes in the mouse are examined over a 25-year period. Detected by skin graft rejections, the mutations were screened in inbred and hybrid mice from a continuously maintained and monitored colony and from a regularly supplied set of mice provided from the National Cancer Institute for monitoring of genetic integrity. Twenty-five H2 mutations were recovered, involving the K, D, L, and Ab loci, as well as over 80 mutations of non-H2 histocompatibility genes. Aside from a single allele at a single locus (H2-Kb), the spontaneous mutation rate of H2 class I genes appears to be equivalent to that found estimated for non-H2 histocompatibility genes, and comparable to rates reported for a variety of mouse genes. This is in contrast with previous suggestions that H2 genes mutate at orders of magnitude greater than do "average" mammalian genes. The discrepancy is attributed to the H2-Kb gene which accounts for over half of all reported H2 mutations and which mutates spontaneously at a rate of 1-2 x 10(-4) per gene per generation. Furthermore, over half of the spontaneous H2-Kb mutations result in a single mutant phenotype (the "bg" group) which involve similar changes at amino acid residues 116 and 121. Thus, the high spontaneous mutation rate for H2-Kb appears to be the exception among major histocompatibility genes, rather than the rule.

Animals↗
PubMed1986

Distinct effect of forskolin and interferon-gamma on cell proliferation and regulation of histocompatibility antigen expression in hematopoietic cells.

The adenylate cyclase activator, forskolin, was found to induce expression of class I and class II major histocompatibility complex antigens in a B precursor cell line, Reh, as well as in a B lymphoid cell line, Raji. No such effect was, however, observed when the promyelocytic cells line HL-60 was treated with either forskolin or the cAMP analogue 8-bromoadenosine cyclic monophosphate. As expected, all three cell lines showed reduced proliferation upon forskolin treatment. Forskolin induced expression of class I and class II major histocompatibility complex antigens in cell lines not affected by interferon-gamma and vice versa, indicating that cAMP is not involved in the regulation of histocompatibility antigens by interferon-gamma. We also compared the effect of interferon-gamma and 12-O-tetradecanoylphorbol 13-acetate on major histocompatibility complex class I and class II expression, and despite differences in the response on the tested cell lines, we can not at this point exclude the possibility that protein kinase C is involved in the action of interferon-gamma.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1991

Minor histocompatibility antigens.

Histocompatibility antigens have been studied for over 50 years because they form a major obstacle to clinical transplantation. Human minor histocompatibility antigens remain ill-defined, but minor histocompatibility loci have been mapped on nearly every mouse chromosome. Recent molecular definition of several transplantation antigens suggests that they are by-products of an immune system poised to present viral antigens, and a mutation in any gene may give rise to a new minor histocompatibility antigen.

Amino Acid Sequence↗
PubMed2005

Histocompatibility testing predicts acute rejection risk in early corticosteroid withdrawal regimens.

UNLABELLED: Histocompatibility testing has been shown to predict acute rejection risk in steroid-based immunosuppression. However, little evidence exists of its ability to predict acute rejection risk in corticosteroid-free patients, with no evidence in early corticosteroid withdrawal (CSWD) under modern immunosuppression. The purpose of this study was to evaluate the ability of histocompatibility testing to identify patients at high risk for acute rejection after early CSWD. METHODS: One hundred eighty-one patients were entered into six IRB-approved early CSWD regimens. Histocompatibility testing included serologic PRA, flow cytometric PRA testing by Class I and Class II MHC beads, and B cell crossmatching with pronase treatment. All rejection episodes were biopsy proven, and grading was assigned using Banff criteria. Influence of individual tests was examined using Chi square univariate and multivariate logistic regression analysis. RESULTS: Median follow-up was 23.5 months (range 7-48 months). Of 181 patients, 16% were repeat transplant recipients, 36% received deceased donor renal transplants, 48% received living related donor renal transplants, and 16% received living unrelated transplants. Overall patient survival was 97%, and death-censored graft survival was 96.5%. Acute rejection rates in the entire follow-up period were 17.7%. 12.4% in primary transplant recipients and 37% in repeat transplant recipients. Multivariate analysis revealed that HLA AB and DR locus mismatching were associated with increased acute rejection risk. Similarly, serologic PRA analysis predicted acute rejection risk; however, flow cytometry crossmatching did not predict acute rejection risk. The greatest single influence on acute rejection risk appeared to be a flow cytometric B cell crossmatch (7.94-fold increased risk). In conclusion, histocompatibility testing can identify patients at high risk for acute rejection following early CSWD. HLA matching, serologic PRA testing, and flow cytometry-based B cell crossmatching can all be used to predict acute rejection risk.

Adrenal Cortex Hormones↗
PubMed1997

Specific effects of estrogen on growth factor and major histocompatibility complex class II antigen expression in rat aortic allograft.

OBJECTIVE: Transplant arteriosclerosis is the major determinant for long-term survival of cardiac transplants. Estradiol treatment inhibits transplant arteriosclerosis. The objective of this study is to determine, in the absence of immunosuppression, the temporal effect of estradiol treatment on the expression of insulin-like growth factor, platelet-derived growth factor, basic fibroblast growth factor, and major histocompatibility complex class II antigen in rat aortic allografts. METHODS: Orthotopic abdominal aortic allograft transplantation was performed in male rats with Brown-Norway rats used as donors and Lewis rats as recipients. The recipients (n = 50) were treated with estradiol 20 micrograms/kg per day or placebo by osmotic minipump for 2 days before the operation and until they were put to death on postoperative days 1, 3, 7, 14, or 21. The allografts were harvested and insulin-like growth factor, platelet-derived growth factor, basic fibroblast growth factor, and major histocompatibility complex class II antigen expression were determined by immunohistochemical staining. Myointimal thickening was measured by morphometric analysis. RESULTS: In the placebo-treated group, insulin-like growth factor protein progressively increased in all three layers of the allograft, whereas platelet-derived growth factor protein peaked at day 3 and basic fibroblast growth factor protein increased only moderately. Estradiol treatment inhibited the continuous increase in insulin-like growth factor expression, the peak in platelet-derived growth factor expression at day 3, the moderate-basic fibroblast growth factor increase at day 21, and major histocompatibility complex class II antigen expression in all three layers of the allograft at day 21. Intimal thickening of allografts from estradiol-treated recipients was twofold to threefold less than that of the placebo-treated recipients at day 21. CONCLUSION: The development of transplant arteriosclerosis is associated with an early alloimmune response involving sustained increase in insulin-like growth factor expression. Estradiol treatment of the recipient inhibits transplant arteriosclerosis and suppresses insulin-like growth factor and major histocompatibility complex class II antigen expression but not platelet-derived growth factor or basic fibroblast growth factor in all three layers of the allograft during the early posttransplantation alloimmune rejection phase.

Animals↗
PubMed1979

Familial urinary tract anomalies: association with the major histocompatibility complex in man.

Histocompatibility typing of a family with 15 members and a history of ureteropelvic junction stenosis and 4 families with 23 members and a history of vesicoureteral reflux revealed that these anomalies of the urinary tract may be hereditary and segregate with histocompatibility haplotype within a family. Thus, a close linkage of childhood reflux and ureteral stenosis with that of the major histocompatibility complex of man is suggested. If confirmed by further family studies it will place the gene(s) for vesicoureteral reflux and ureteral stenosis on the 6th pair of human chromosome and open the possibility of using histocompatibility typing as a marker for these anomalies within a family.

Adolescent↗
PubMed2002

Feasibility of using genetic linkage analysis to identify the genes encoding T cell-defined minor histocompatibility antigens.

We have evaluated the utility of genetic linkage analysis to identify genes that encode minor histocompatibility antigens using vaccinia virus vectors as a simple and convenient method for transient expression of class I MHC molecules in lymphoblastoid cell lines. As a test case, we used a CTL clone that recognizes HA-8, a minor histocompatibility antigen encoded by the KIAA0020 gene and presented by HLA-A*0201. EBV-transformed B cell lines from individuals in three large pedigrees from the CEPH reference family collection were infected with a recombinant vaccinia virus vector encoding an HLA-A*0201 transgene, which led to high level expression of the MHC restricting allele HLA-A*0201 on the cell surface. HA-8 expression in the vaccinia-infected target cells was then determined using standard in vitro cytotoxicity assays. Pairwise linkage analysis of the segregation of HA-8 expression in these pedigrees demonstrated that the HA-8 gene was tightly linked with a cluster of marker loci located on the distal portion of chromosome 9p. Analysis of 9p marker haplotypes for individuals in the three families identified several individuals with recombinant haplotypes, and these recombination events were used to refine the precision of the HA-8 gene localization further. The data collectively indicate that the HA-8 gene is localized to a 10.3 cM (corresponding to 3.9 Mb) interval of distal 9p that is thought to encode at least 11 genes, including KIAA0020. These results demonstrate that linkage analysis can be used to map minor histocompatibility genes with high precision and accuracy. Over the next years, refinement and annotation of the human genome sequence will undoubtedly increase the utility of linkage analysis as a tool for identifying minor histocompatibility antigen genes.

Antigens, Surface↗
PubMed1981

Expression of major histocompatibility antigens on pancreatic islet cells.

Insulin-dependent diabetes mellitus is often accompanied by manifestations of autoimmunity and is frequently associated with certain HLA haplotypes, predominantly DR3 and DR4. Because the major histocompatibility antigens are important determinants of the immune response in various tissues, we have investigated their expression on the pancreatic islet cells. Human, mouse, or rat islets of Langerhans, as well as lymphocytes or other differentiated cells, were biosynthetically labeled with radioactive amino acids, lysed in detergent, and immunoprecipitated with several antisera specific for major histocompatibility antigenic groups. The immunoprecipitates were analyzed by NaDodSo4/polyacrylamide gel electrophoresis under reducing conditions followed by autoradiography. The major histocompatibility antigens corresponding to the H-2 K,D molecules in mice, the H1-A in rats, and the HLA-A, -B, and -C in humans were precipitated from both islet and lymphocyte lysates and were accompanied by beta 2-microglobulin. Binding of H-2 antibodies to islet cells was also confirmed by a radioligand assay using 125I-labeled protein A and by indirect immunofluorescence. Analyses in the fluorescence-activated cell sorter revealed that greater than 95% of the cells in the beta-cell-rich fraction were fluorescent, providing further evidence that the pancreatic beta cells express the major histocompatibility antigens. Monoclonal antibodies or mouse alloantisera against HLA-DR or Ia antigens did not react with labeled pancreatic islet cell proteins.

Animals↗
PubMed1989

Inhibition of insulin receptor phosphorylation by peptides derived from major histocompatibility complex class I antigens.

Peptides from the alpha 1 region (residues 61-85) of the D and K molecules of the major histocompatibility complex class I antigens inhibit insulin-induced tyrosine kinase activity of the purified human insulin receptors (IRs) as measured both by autophosphorylation and IR-mediated substrate [poly(Glu,Tyr)] phosphorylation. Half-maximal effect of the Dk-(61-85) peptide on IR autophosphorylation is obtained at 1.2 microM, and almost complete inhibition of IR kinase activity is obtained at 10 microM peptide. The corresponding K kappa-(61-85) peptide has a significantly weaker effect on autophosphorylation. No such effects are observed with nine peptides of similar length, but unrelated to major histocompatibility complex class I antigens. Neither of the major histocompatibility complex class I-derived peptides has any effect on the constitutively active kinase of a genetically engineered cytoplasmic IR domain. Further, insulin binding to IR is unaltered in the presence of the major histocompatibility complex class I-derived peptides. The inhibitory activity of the peptides on insulin-induced IR phosphorylation facilitated the observation that IRs require insulin to become substrate for an independent tyrosine kinase. In the presence of an inhibitory peptide, the constitutively active cytoplasmic IR kinase domain only phosphorylates the intact IR in the presence of insulin. We conclude that the tyrosine kinase activity of IRs may be altered by peptide interaction at an allosteric site and, moreover, IRs require insulin to assume a conformation permitting phosphorylation by an independent kinase.

Allosteric Site↗
PubMed1971

Specific immune response genes of the guinea pig. 3. Linkage of the GA and GT immune response genes to histocompatibility genotypes in inbred guinea pigs.

The ability of guinea pigs to form immune responses specific for each of the random copolymers, L-glutamic acid and L-alanine (GA) and L-glutamic acid and L-tyrosine (GT), is under the control of distinct autosomal dominant genes. By testing for the ability to respond to these copolymers among the progeny from the reciprocal backcross mating of responder (2 x 13)F(1) animals with the appropriate nonresponder parental strain, we have demonstrated that different unigenic autosomal dominant traits control the ability to respond to GA and GT respectively. The data further shows that the GA gene is linked to the poly-L-lysine (PLL) gene and to the locus determining the major strain 2 histocompatibility specificities and that the GT gene is linked to the locus controlling the expression of major strain 13 histocompatibility specificities. Analysis of the inheritance of the GT and PLL genes among the offspring from a mating of responder (2 x 13)F(1) guinea pigs with random-bred guinea pigs unable to respond to GT or PLL demonstrate that these genes segregate away from each other. Thus, the PLL gene and the genes to which it is linked, the GA gene and the major strain 2 histocompatibility locus, behave as alleles or pseudoalleles to the GT gene and the major strain 13 histocompatibility locus.

Alanine↗
PubMedDate not supplied

Genetic polymorphism of a bovine t-complex gene (TCP1) linkage to major histocompatibility genes.

Southern blot analysis of genomic cattle DNA was carried out using murine cDNA probes representing the Tcp-1 gene of the t complex. Excellent cross-hybridization was obtained, and the probes apparently hybridized to at least two bovine TCP1 genes. Two independent restriction fragment length polymorphisms, each composed of two allelic variants, were detected; the inheritance of the restriction fragment length polymorphisms was confirmed by family data. One of the restriction fragment length polymorphisms, designated TCP1B, was evidently due to a gene duplication and was revealed with any restriction enzyme used. The duplication was found in three different cattle breeds investigated. Family segregation data indicated that TCP1B is linked to major histocompatibility complex genes. The result was consistent with close linkage to the major histocompatibility complex class II DO beta gene, whereas a fairly high recombination frequency was indicated between TCP1B/DO beta and other major histocompatibility complex genes. The result assigns TCP1B to a bovine linkage group previously comprising major histocompatibility complex class I and class II genes and blood group locus M. The similarity between this linkage group and parts of mouse chromosome 17 (t-H-2) and human chromosome 6 (TCP1-HLA) is discussed.

Animals↗
PubMed1985

Comparison of altered expression of histocompatibility antigens with altered immune function in murine spleen cells treated with ultraviolet radiation and/or TPA.

Previous studies in our laboratory demonstrated that several treatments that inhibited the ability of cells to stimulate the mixed lymphocyte reaction (MLR) also blocked the shedding of histocompatibility antigens and Ia antigens from murine spleen cells. In the present studies, one of these treatments, ultraviolet radiation (UV), was shown to cause an initial loss in the density of H-2K, IA, and IE antigens prior to the block in shedding observed after culture of these cells. Further analysis revealed that the UV-induced loss of antigens could be prevented by the presence of colchicine during irradiation. Biosynthetic analyses revealed the IA antigen synthesis was also inhibited in the UV-irradiated cells. Examination of the effects of a second agent, 12-0-tetradecanoylphorbol-13-acetate (TPA) on the turnover of histocompatibility antigens revealed that the biosynthesis and shedding of these antigens were accelerated by this agent. However, addition of TPA to UV-irradiated cells did not result in a reversal of the UV-induced block in biosynthesis of IA antigens. Results of immune function assays correlated with the biochemical studies: UV-irradiation inhibited the generation of the MLR, but TPA enhanced this reaction, and addition of TPA to mixed lymphocyte cultures with UV-irradiated stimulators did not reverse the UV-induced inhibition. These results suggest that, although the turnover of histocompatibility antigens may be affected by TPA and UV in an antagonistic fashion, additional factors other than the expression of histocompatibility antigens are operating in the inhibition of stimulation of an MLR by UV radiation or its enhancement by TPA.

Animals↗
PubMed1985

Adoptive immunotherapy of metastatic B16 melanoma with allogeneic immune cells sensitized to minor histocompatibility antigens.

Host mice bearing pulmonary metastases of B16 melanoma were treated by adoptive immunotherapy with allogeneic donor lymphocytes. Rejection of the allogeneic donor cells by the host was delayed by pretreatment immunosuppression of the host with cyclophosphamide and selection of donors that were matched at the major histocompatibility complex (MHC) but disparate for background minor histocompatibility genes. Adoptively transferred normal nonimmune donor cells exhibited no therapeutic activity. However, allogeneic MHC-matched donor cells that were primed in vivo and secondarily sensitized in vitro to host minor histocompatibility antigens expressed on normal lymphocytes were cytotoxic to B16 tumor cells in vitro and mediated a dose-dependent antitumor effect in vivo following i.v. infusion. The therapeutic activity of sensitized allogeneic cells, which presumably reflected recognition of minor histocompatibility antigens expressed both on normal host tissues and on malignant B16 tumor cells, was not associated with any detectable toxicity to these transiently immunosuppressed tumor-bearing hosts.

Animals↗
PubMed1988

An A-chain ricin immunotoxin targeted against rat class II major histocompatibility complex molecules. In vitro and in vivo effects.

Studies reported here have demonstrated that an antirat class II major histocompatibility complex molecule A-chain ricin immunotoxin could specifically remove, in a dose-dependent manner, the cells capable of stimulating the rat mixed lymphocyte reaction, an in vitro model of transplant rejection. It was further demonstrated that administration of a monoclonal antibody against class II major histocompatibility complex molecules to isolated rat pancreas grafts by hypothermic perfusion resulted in the targeting of cells bearing class II major histocompatibility complex molecules. But administration of the immunotoxin to isolated pancreases in a similar manner did not prolong their survival when allografted across a major histocompatibility barrier.

Animals↗
PubMed2003

Histocompatible miniature swine: an inbred large-animal model.

Three herds of miniature swine, each homozygous for a different set of alleles at the major histocompatibility complex (MHC), and five intra-MHC recombinant strains, have been reported by the authors' laboratory. One herd (SLAdd) was selected for further inbreeding to achieve a histocompatible line. It has undergone seven additional generations of sequential brother-sister or father-daughter matings (termed G7). To determine the level of histocompatibility of these animals, the authors performed skin and heart transplantation without immunosuppression. In contrast to MHC-matched, minor antigen-mismatched animals that rejected skin in 11 days (median survival time [MST], n=6) and hearts in 35 days (MST, n=4), G7 animals accepted skin for greater than 340 days (>340, >448, and >677 days) and hearts for greater than 265 days (>265 and >269 days). Nevertheless, rejection of second grafts could be induced by sensitization, indicating that weak minor antigens remain, requiring further inbreeding to achieve full histocompatibility. We conclude that G7 animals are sufficiently inbred to accept first set skin and heart grafts indefinitely.

Animals↗
PubMed1986

Cutaneous acute graft-versus-host disease to minor histocompatibility antigens in a murine model: histologic analysis and correlation to clinical disease.

Graft-versus-host disease (GVHD) can occur in bone marrow-transplant recipients even when donor and host are identically matched at the major histocompatibility complex. GVHD in this context presumably arises because of differences in minor histocompatibility antigens. Murine GVHD to minor histocompatibility antigens has been studied in an effort to determine whether skin is a target of the immune response in this model system. T cell-depleted marrow cells (10(7)) from B10.BR (H-2k) mice were supplemented with varying numbers of nylon wool-enriched splenic B10.BR T cells and transplanted intravenously into irradiated (1100 R) CBA (H-2k) mice. Sequential biopsies of ear skin were obtained at weekly intervals over a 7-week period. Histopathologic evaluation revealed basal cell layer vacuolization, exocytosis, and satellitosis of mononuclear cells in the epidermis. Dyskeratosis was observed only in animals receiving T cells, and proved to be the most reliable histologic parameter of disease with the number of dyskeratotic cells per linear millimeter of epidermis correlating both with severity of clinical disease and with the number of transplanted T cells. Ultrastructural examination revealed exocytosis of mononuclear cells into the epidermis where they were frequently apposed to degenerating and necrotic keratinocytes. These data indicate that the skin is an informative target organ for study of experimental GVHD to minor histocompatibility antigens.

Acute Disease↗