Role of Class-II Major Histocompatibility Complex (MHC)-Antigen–Positive Donor Leukocytes in Transfusion-Induced Alloimmunization to Donor Class-I MHC Antigens

Blood ◽  
1998 ◽  
Vol 92 (2) ◽  
pp. 690-694
Author(s):  
K.J. Kao ◽  
M.L.U. del Rosario
Keyword(s):  
Immune Response ◽  
Peripheral Blood ◽  
Class Ii ◽  
Class I ◽  
Mononuclear Leukocytes ◽  
Class I Mhc ◽  
Mhc Antigens ◽  
Mhc Molecules ◽  
Class Ii Mhc ◽  
Mhc Antigen

It has been shown that peripheral-blood mononuclear leukocytes (MNL) are responsible for transfusion-induced alloimmunization to donor major histocompatability complex (MHC) antigens. However, it is not known which subset of MNL is responsible for this immune response. Because elimination of class-II MHC antigen-positive passenger leukocytes effectively prolongs the survival of allografts, it has been hypothesized that class-II positive MNL are responsible for immunizing transfusion recipients to donor MHC antigens. To test this hypothesis, two different approaches were used. First, we compared the alloantigenicity of BALB/c mice (H-2d) peripheral blood MNL before and after depletion of class-II positive cells. CBA mice (H-2k) were used as transfusion recipients. Antibody development to donor class-I H-2 antigens was determined by flow cytometry and enzyme-linked immunoassay. After four weekly transfusions of MNL depleted for class-II positive cells, only 25% of recipient mice developed antibodies to donor H-2d antigens. In contrast, all mice transfused with control MNL became immunized. Second, we studied the alloantigenicity of peripheral MNL from C57BL/6 mice (H-2b) with homozygous deficiency of class-II MHC molecules in H-2 disparate recipient mice. After transfusions with class-II MHC molecule-deficient MNL, 0% of BALB/c, 40% of C57BR, and 25% of CBA-recipient mice developed antibodies to donor H-2b antigen. All control recipient mice were immunized. The antibody activities of the controls were also higher than those in the treatment group who became immunized. Thus, our study shows that class-II MHC antigen-positive MNL play a significant role in transfusion-induced alloimmunization to donor class-I MHC antigens. The results also support the hypothesis that direct antigen presentation by donor class-II positive MNL to the immune system of transfusion recipients is critical for the initiation of humoral immune response to donor MHC antigens.

Role of Class-II Major Histocompatibility Complex (MHC)-Antigen–Positive Donor Leukocytes in Transfusion-Induced Alloimmunization to Donor Class-I MHC Antigens

Blood ◽  
1998 ◽  
Vol 92 (2) ◽  
pp. 690-694 ◽  
Author(s):  
K.J. Kao ◽  
M.L.U. del Rosario
Keyword(s):  
Immune Response ◽  
Peripheral Blood ◽  
Class Ii ◽  
Class I ◽  
Mononuclear Leukocytes ◽  
Class I Mhc ◽  
Mhc Antigens ◽  
Mhc Molecules ◽  
Class Ii Mhc ◽  
Mhc Antigen

Abstract It has been shown that peripheral-blood mononuclear leukocytes (MNL) are responsible for transfusion-induced alloimmunization to donor major histocompatability complex (MHC) antigens. However, it is not known which subset of MNL is responsible for this immune response. Because elimination of class-II MHC antigen-positive passenger leukocytes effectively prolongs the survival of allografts, it has been hypothesized that class-II positive MNL are responsible for immunizing transfusion recipients to donor MHC antigens. To test this hypothesis, two different approaches were used. First, we compared the alloantigenicity of BALB/c mice (H-2d) peripheral blood MNL before and after depletion of class-II positive cells. CBA mice (H-2k) were used as transfusion recipients. Antibody development to donor class-I H-2 antigens was determined by flow cytometry and enzyme-linked immunoassay. After four weekly transfusions of MNL depleted for class-II positive cells, only 25% of recipient mice developed antibodies to donor H-2d antigens. In contrast, all mice transfused with control MNL became immunized. Second, we studied the alloantigenicity of peripheral MNL from C57BL/6 mice (H-2b) with homozygous deficiency of class-II MHC molecules in H-2 disparate recipient mice. After transfusions with class-II MHC molecule-deficient MNL, 0% of BALB/c, 40% of C57BR, and 25% of CBA-recipient mice developed antibodies to donor H-2b antigen. All control recipient mice were immunized. The antibody activities of the controls were also higher than those in the treatment group who became immunized. Thus, our study shows that class-II MHC antigen-positive MNL play a significant role in transfusion-induced alloimmunization to donor class-I MHC antigens. The results also support the hypothesis that direct antigen presentation by donor class-II positive MNL to the immune system of transfusion recipients is critical for the initiation of humoral immune response to donor MHC antigens.

MHC Sınıf I ve MHC Sınıf II Gen Düzenlenmesi

2020 ◽  
Vol 8 (3) ◽  
pp. 144-156
Author(s):  
Şule KARATAŞ ◽  
Fatma SAVRAN OĞUZ
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Gene Regulation ◽  
Mhc Class I ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Class I ◽  
Mhc Molecules ◽  
Class Ii Mhc ◽  
Regulation Mechanisms

Introduction: Peptides obtained by processing intracellular and extracellular antigens are presented to T cells to stimulate the immune response. This presentation is made by peptide receptors called major histocompatibility complex (MHC) molecules. The regulation mechanisms of MHC molecules, which have similar roles in the immune response, especially at the gene level, have significant differences according to their class. Objective: Class I and class II MHC molecules encoded by MHC genes on the short arm of the sixth chromosome are peptide receptors that stimulate T cell response. These peptides, which will enable the recognition of the antigen from which they originate, are loaded into MHC molecules and presented to T cells. Although the principles of loading and delivering peptides are similar for both molecules, the peptide sources and peptide loading mechanisms are different. In addition, class I molecules are expressed in all nucleated cells while class II molecules are expressed only in Antigen Presentation Cells (APC). These differences; It shows that MHC class I is not expressed by exactly the same transcriptional mechanisms as MHC class II. In our article, we aimed to compare the gene expressions of both classes and reveal their similarities and differences. Discussion and Conclusion: A better understanding of the transcriptional mechanisms of MHC molecules will reveal the role of these molecules in diseases more clearly. In our review, we discussed MHC gene regulation mechanisms with presence of existing informations, which is specific to the MHC class, for contribute to future research. Keywords: MHC class I, MHC class II, MHC gene regulation, promoter, SXY module, transcription

scholarly journals 115 CYTOLOGICAL ANALYSIS OF HEPATIC GENE EXPRESSION AND IMMUNOLOGICAL RESPONSE OF MHC ANTIGENS IN MOUSE AMNIOTIC EPITHELIAL CELLS

2005 ◽  
Vol 17 (2) ◽  
pp. 208
Author(s):  
T. Mitani ◽  
T. Nagai ◽  
D. Suzuki ◽  
Y. Ukida ◽  
H. Kato ◽  
...  
Keyword(s):  
Class Ii ◽  
Class I ◽  
Hepatic Gene Expression ◽  
Rt Pcr ◽  
Mhc Antigens ◽  
Mhc Molecules ◽  
Hepatic Cells ◽  
Class Ii Mhc ◽  
Class Ii Mhc Antigens ◽  
Ifn Γ

Human amniotic epithelial cells (hAECs) have been reported to have unique properties. They express almost no class I and class II MHC antigens and lack response to interferon-γ (IFN-γ) which mediates the expression of those MHC molecules. Moreover, hAECs express some genes characteristic of hepatic cells. Therefore, hAECs seem to have multipotency and are expected to substitute for hepatic tissues in part. We aimed to develop the experimental model for investigating AECs in mice (mAECs). In this study, we examined the induction of MHC molecules by IFN-γ and the hepatic gene expression in mAECs. Murine amniotic membranes were collected from C57BL/6J females at 17.5 days of gestation. They were digested by 0.03% hyaluronidase followed by 0.2% collagenase treatment. Dissociated mAECs were cultured on dishes in DMEM supplemented with 10% FBS at 37°C under 5%CO2 in air. Embryonic fibroblasts (EFs) collected from C57BL/6J fetuses at 13.5 dpc were cultured in the same condition as mAECs. In Experiment I, the effect of IFN-γ on induction of MHC molecules in mAECs was examined. mAECs and EFs cultured in the presence or absence of IFN-γ at 1 × 103 U mL−1 for 72 h were recovered and incubated with FITC-conjugated antibodies against mouse H-2 MHC class I or I-A/I-E MHC class II antigens. The cells were analyzed by flow cytometry. In Experiment II, the expression of the genes in mAECs was examined by RT-PCR. mRNA was purified from adult liver, EFs, fresh mAECs, and mAECs cultured for 5 days. As the genes characteristic for hepatic cells, HNF-3α, HNF-3β, HNF-3γ, HNF-4, transthyretin (TTR), albumin, α-fetoprotein (AFP), glucose-6-phosphatase (G6P), and asialoglycoprotein receptor-1 (Asgr1) were examined. In Experiment I, cell-surface expression of class I and class II MHC antigens in response to IFN-γ was observed weakly in mAECs as compared to EFs, suggesting different property in hAECs which lack the expression of those antigens. In Experiment II, RT-PCR analysis showed that all of the genes except G6P were expressed in fresh mAECs. However, the expression of transcription factors such as HNF-3α, HNF-3β, HNF-4, and TTR, serum proteins such as albumin and AFP, and Asgr1 decreased after in vitro culture, contrary to the case of hAECs in which, for example, albumin appeared after cultivation. In conclusion, it was evident that mAECs have quite different properties, both in the inductivity of MHC molecules and the expression of hepatic genes, from hAECs. This work was supported by Wakayama Prefecture Collaboration of Regional Entities for the Advancement of Technological Excellence of the JST, and by a Grant-in-Aid for the 21st Century COE Program of the Japan MEXT.

Electron microscopy analysis of degenerating pancreatic ß cells in transgenic mice expressing the MHC Class I antigen Dd

1990 ◽  
Vol 48 (3) ◽  
pp. 548-549
Author(s):  
T. A. Stewart ◽  
D. Liggitt ◽  
S. Pitts ◽  
L. Martin ◽  
M. Siegel ◽  
...  
Keyword(s):  
Type I Diabetes ◽  
Disease Process ◽  
Class Ii ◽  
Class I ◽  
Type I ◽  
Aberrant Expression ◽  
Mhc Molecules ◽  
Endogenous Insulin ◽  
Class Ii Mhc ◽  
Ifn Γ

Insulin-dependant (Type I) diabetes mellitus (IDDM) is a metabolic disorder resulting from the lack of endogenous insulin secretion. The disease is thought to result from the autoimmune mediated destruction of the insulin producing ß cells within the islets of Langerhans. The disease process is probably triggered by environmental agents, e.g. virus or chemical toxins on a background of genetic susceptibility associated with particular alleles within the major histocompatiblity complex (MHC). The relation between IDDM and the MHC locus has been reinforced by the demonstration of both class I and class II MHC proteins on the surface of ß cells from newly diagnosed patients as well as mounting evidence that IDDM has an autoimmune pathogenesis. In 1984, a series of observations were used to advance a hypothesis, in which it was suggested that aberrant expression of class II MHC molecules, perhaps induced by gamma-interferon (IFN γ) could present self antigens and initiate an autoimmune disease. We have tested some aspects of this model and demonstrated that expression of IFN γ by pancreatic ß cells can initiate an inflammatory destruction of both the islets and pancreas and does lead to IDDM.

Phosphorylation of class I but not class II MHC molecules by membrane-localized protein kinase C

1989 ◽  
Vol 26 (12) ◽  
pp. 1095-1104 ◽  
Author(s):  
Teresa Burke ◽  
Karen Pollok ◽  
William Cushley ◽  
E. Charles Snow
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Class Ii ◽  
Class I ◽  
Mhc Molecules ◽  
Kinase C ◽  
Class Ii Mhc

Diversity of MHC class II DAB1 in the koala (Phascolarctos cinereus)

2012 ◽  
Vol 60 (1) ◽  
pp. 1 ◽  
Author(s):  
Sarah E. Jobbins ◽  
Claire E. Sanderson ◽  
Joanna E. Griffith ◽  
Mark B. Krockenberger ◽  
Katherine Belov ◽  
...  
Keyword(s):  
Immune Response ◽  
Mhc Class Ii ◽  
Genetic Research ◽  
Class Ii ◽  
Population Diversity ◽  
Environment Interaction ◽  
Phascolarctos Cinereus ◽  
Mhc Molecules ◽  
Adaptive Immune ◽  
Class Ii Mhc

The host immune response is an important factor determining the outcome of the host–pathogen–environment interaction. At the gateway between the innate and adaptive immune systems are MHC molecules, which facilitate antigen presentation to T lymphocytes, and initiate the adaptive immune response. Despite their integral role in adaptive immunity, the genes encoding class II MHC molecules have not been examined directly in koalas. Furthermore, indirect historical evidence suggests that this species might lack functional diversity in class II MHC genes, with potential implications for disease susceptibility. We have examined diversity in the β chain genes of the koala class II MHC DA gene family and identified 23 alleles, including several atypical alleles. The levels of diversity observed are consistent with other marsupial and eutherian species, and do not support the paucity of variation suggested by the early literature. These findings are relevant to the conservation management of koalas and provide both a benchmark for maintaining population diversity and a platform for further conservation genetic research in this species.

scholarly journals Depletion of CD8+ cells in human thymic medulla results in selective immune deficiency.

1989 ◽  
Vol 170 (6) ◽  
pp. 2177-2182 ◽  
Author(s):  
C M Roifman ◽  
D Hummel ◽  
H Martinez-Valdez ◽  
P Thorner ◽  
P J Doherty ◽  
...  
Keyword(s):  
T Cells ◽  
Peripheral Blood ◽  
Inbred Mice ◽  
Pneumocystis Carinii ◽  
Antigen Expression ◽  
Class I ◽  
Class I Mhc ◽  
Cd8 Cells ◽  
Mhc Antigen ◽  
Selection Of

CD8 molecules expressed on the surface of a subset of T cells participate in the selection of class I MHC antigen-restricted T cells in the thymus, and in MHC-restricted immune responses of mature class I MHC antigen-restricted T cells. Here we describe an immune-deficient patient with lack of CD8+ peripheral blood cells. The patient presented with Pneumocystis carinii pneumonia and was unable to reject an allogeneic skin graft, but had normal primary and secondary antibody responses. Examination of the patient's thymus revealed that the loss of CD8+ cells occurred during intrathymic differentiation: the patient's immature cortical thymocytes included both CD4+ and CD8+ cells while the mature medullary cells expressed the CD4 but not the CD8 protein on their surface. Northern blot and polymerase chain reaction analyses revealed the presence of CD8 alpha and beta mRNA in the patient's thymus but not in the peripheral blood. Both class I MHC antigen expression and the expressed TCR V beta repertoire are normal in this patient. These data are consistent with an impaired selection of CD8+ cells in the patient's thymus and support the role of the CD8 surface protein in thymic selection previously characterized in genetically manipulated and inbred mice.

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