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MHC Class I Molecules (mhc + class_i_molecule)

Distribution by Scientific Domains

Medical Sciences	78%

Distribution within Medical Sciences

Immunology	64%
Oncology & Radiotherapy	17%

Selected Abstracts

Immune modulation of HLA-G dimer in maternal-fetal interface

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2007
Kimiko Kuroki
Abstract HLA-G is a non-classical human MHC class I molecule, which has several characteristics distinct from classical MHC, such as low polymorphism and restricted tissue distribution. HLA-G is expressed on placenta, thymus and some tumors. At the maternal-fetal interface, trophoblasts do not express major classical MHC class I molecules (MHCI), HLA-A and -B, to prevent normal T cell responses. Instead, HLA-G is expressed and can suppress a wide range of immune responses by binding to inhibitory immune cell surface receptors, such as leukocyte Ig-like receptor (LILR) B1 and LILRB2. HLA-G exists in various forms, including ,2m-associated or -free disulfide-linked dimers that can be expressed either at the cell surface or in soluble form. However, until recently the physiological role of these different molecular forms has been unclear. In this issue of the European Journal of Immunology, one article demonstrates that the disulfide-linked homodimer of ,2m-associated HLA-G is the major fraction expressed by trophoblast cells. The HLA-G dimer modulates the function of LILRB1-expressing antigen-presenting cells by principally binding to LILRB1. On the other hand, another recent report showed that ,2m-free disulfide-linked HLA-G dimers are produced by villous cytotrophoblast cells. Taken together, these results provide strong evidence in support of the hypothesis that HLA-G dimers play a role in immune suppression at the maternal-fetal interface. Further in-depth investigation will help to clarify the precise mechanism of HLA-G receptor recognition and signaling in vivo and the role of these interactions in successful reproduction. See accompanying article: http://dx.doi.org/10.1002/eji.200737089 [source]

ORIGINAL ARTICLE: Suppression of Mamu-AG by RNA Interference

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2009
Jessica G. Drenzek
Problem, The role of placental major histocompatibility complex (MHC) class I molecules in pregnancy is not well understood. Mamu-AG, the rhesus monkey homology of human leukocyte antigen (HLA)-G expressed in the human placenta, was targeted for degradation by RNA interference (RNAi), a powerful tool to aid in determining gene function, to determine the effect that this knockdown has on NK cell function. Method of study, A series of potential target short hairpin RNA (shRNA) sequences to suppress Mamu-AG expression was screened, which identified an optimal sequence to use in transfection experiments. Knockdown in two different Mamu-AG-expressing cell lines was measured by flow cytometry. Cytotoxicity assays were performed to correlate Mamu-AG expression with NK cell cytotoxicity. Results, Decreased expression of Mamu-AG by short interfering RNA (siRNA) (70,80%) in cell types tested was associated with increased lysis of Mamu-AG target cells. Conclusion, Target sequences have been identified that knocked down Mamu-AG expression by RNAi and increased lysis by NK cells. This supports the concept that NK cell receptors recognize this placental non-classical MHC class I molecule. [source]

Complex assembly, crystallization and preliminary X-ray crystallographic studies of duck MHC class I molecule

ACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 1 2010
Jianhua Zhang
In order to understand the biological properties of the immune systems of waterfowl and to establish a system for structural studies of duck class I major histocompatibility complex (DuMHC I), a complex of DuMHC I with duck ,2 -microglobulin (Du,2m) and the peptide AEIEDLIF (AF8) derived from H5N1 NP residues 251,258 was assembled. The complex was crystallized; the crystals belonged to space group C2221, with unit-cell parameters a = 54.7, b = 72.4, c = 102.2,Å, and diffracted to 2.3,Å resolution. Matthews coefficient calculation and initial structure determination by molecular replacement showed that the crystals did not contain the whole DuMHC I complex, but instead contained the DuMHC I ,3 domain and a Du,2m molecule (DuMHC I ,3+,2m). Another complex of DuMHC I with the peptide IDWFDGKE derived from a chicken fusion protein also generated the same results. The stable structure of DuMHC I ,3+,2m may reflect some unique characteristics of DuMHC I and pave the way for novel MHC structure-related studies in the future. [source]

Lipid-mediated presentation of MHC class II molecules guides thymocytes to the CD4 lineage

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2009
Satoshi Komaniwa
Abstract Previous studies on the MHC class-specific differentiation of CD4+CD8+ thymocytes into CD4+ and CD8+ T cells have focused on the role of coreceptor molecules. However, CD4 and CD8 T cells develop according to their MHC class specificities even in these mice lacking coreceptors. This study investigated the possibility that lineage is determined not only by coreceptors, but is also guided by the way how MHC molecules are presented. MHC class II molecules possess a highly conserved Cys in their transmembrane domain, which is palmitoylated and thereby associates with lipid rafts, whereas neither palmitoylation nor raft association was observed with MHC class I molecules. The generation of CD4 T cells was impaired and that of CD8 T cells was augmented when the rafts on the thymic epithelial cells were disrupted. This was due to the conversion of MHC class II-specific thymocytes from the CD4 lineage to CD8. The ability of I-Ad molecule to associate with rafts was lost when its transmembrane Cys was replaced. The development of DO11.10 thymocytes recognizing this mutant I-Adm was converted from CD4 to CD8. These results suggest that the CD4 lineage commitment is directed by the raft-associated presentation of MHC class II molecules. [source]

Immune modulation of HLA-G dimer in maternal-fetal interface

Human cytomegalovirus and natural killer-mediated surveillance of HLA class I expression: a paradigm of host,pathogen adaptation

IMMUNOLOGICAL REVIEWS, Issue 1 2001
Miguel López-Botet
Summary: Among various strategies to evade the host immune response, some viruses like human cytomegalovirus (HCMV) interfere with surface MHC class I expression and antigen presentation to T lymphocytes. The ability of natural killer (NK) cells to detect MHC class I molecules through inhibitory receptors can be envisaged as an adaptation of the immune system for responding to such pathological alterations. To fulfil that role, rodents use members of the Ly49 C-type lectin superfamily, whereas primates employ killer immunoglobulin-like receptors and the immunoglobulin-like transcript 2/leucocyte immunoglobulin-like receptor-1 receptor. CD94/NKG2 lectin-like heterodimers represent the most conserved receptor system for MHC class I molecules; by interacting with human HLA-E or murine Qa-1b, CD94/NKG2A inhibitory receptors broadly probe the biosynthesis pathway of other class I molecules. Reciprocally, HCMV has developed mechanisms to evade the NK response while modulating HLA class Ia expression. The ability of HCMV to maintain surface levels of HLA-E and to express an HLA class I surrogate (UL18) are herein discussed in the context of the interplay with human NKR systems. This work was supported by grants FIS 00/0181 and SAF98-0006. We thank Dr A. Angulo for helpful discussion. [source]

Major histocompatibility complex (MHC) class II but not MHC class I molecules are required for efficient control of Strongyloides venezuelensis infection in mice

IMMUNOLOGY, Issue 1pt2 2009
Rosângela M. Rodrigues
Summary Strongyloides stercoralis is an intestinal nematode capable of chronic, persistent infection and hyperinfection of the host; this can lead to dissemination, mainly in immunosuppressive states, in which the infection can become severe and result in the death of the host. In this study, we investigated the immune response against Strongyloides venezuelensis infection in major histocompatibility complex (MHC) class I or class II deficient mice. We found that MHC II,/, animals were more susceptible to S. venezuelensis infection as a result of the presence of an elevated number of eggs in the faeces and a delay in the elimination of adult worms compared with wild-type (WT) and MHC I,/, mice. Histopathological analysis revealed that MHC II,/, mice had a mild inflammatory infiltration in the small intestine with a reduction in tissue eosinophilia. These mice also presented a significantly lower frequency of eosinophils and mononuclear cells in the blood, together with reduced T helper type 2 (Th2) cytokines in small intestine homogenates and sera compared with WT and MHC I,/, animals. Additionally, levels of parasite-specific immunoglobulin M (IgM), IgA, IgE, total IgG and IgG1 were also significantly reduced in the sera of MHC II,/, infected mice, while a non-significant increase in the level of IgG2a was found in comparison to WT or MHC I,/, infected mice. Together, these data demonstrate that expression of MHC class II but not class I molecules is required to induce a predominantly Th2 response and to achieve efficient control of S. venezuelensis infection in mice. [source]

The MHC class I antigen presentation pathway: strategies for viral immune evasion

IMMUNOLOGY, Issue 2 2003
Eric W. Hewitt
Summary Presumably because of the selective pressure exerted by the immune system, many viruses have evolved proteins that interfere with antigen presentation by major histocompatibility complex (MHC) class I molecules. These viruses utilize a whole variety of ingenious strategies to inhibit the MHC class I pathway. Viral proteins have been characterized that exploit bottlenecks in the MHC class I pathway, such as peptide translocation by the transporter associated with antigen processing. Alternatively, viral proteins can cause the degradation or mislocalization of MHC class I molecules. This is often achieved by the subversion of the host cell's own protein degradation and trafficking pathways. As a consequence elucidation of how these viral proteins act to subvert host cell function will continue to give important insights not only into virus,host interactions but also the function and mechanism of cellular pathways. [source]

E5 protein of human papillomavirus type 16 selectively downregulates surface HLA class I

INTERNATIONAL JOURNAL OF CANCER, Issue 2 2005
G. Hossein Ashrafi
Abstract Papillomaviruses have evolved mechanisms that result in escape from host immune surveillance. The E5 protein is expressed early in papillomavirus infection in the deep layers of the infected epithelium. It is localized to the Golgi apparatus (GA) and endoplasmic reticulum. The E5 protein of bovine papillomavirus (BPV) impairs the synthesis and stability of major histocompatibility (MHC) class I complexes and prevents their transport to the cell surface due to retention in the GA. Here we show that human papillomavirus type 16 (HPV-16) E5 also causes the retention of MHC (HLA) class I complexes in the GA and impedes their transport to the cell surface, which is rescued by treatment with interferon. Unlike BPV E5, HPV-16 E5 does not affect the synthesis of HLA class I heavy chains or the expression of the transporter associated with antigen processing TAP. These results show that downregulation of surface MHC class I molecules is common to both BPV and HPV E5 proteins. Moreover, we determined that HPV-16 E5 downregulates surface expression of HLA-A and HLA-B, which present viral peptides to MHC class I-restricted cytotoxic T lymphocytes (CTLs), but not the natural killer (NK) cell inhibitory ligands HLA-C and HLA-E. Selective downregulation of cell surface HLA class I molecules may allow the virus to establish infection by avoiding immune clearance of virus-infected cells by both CTLs and NK cells. [source]

Review: Relaxin Expressed at the Feto,Maternal Interface

REPRODUCTION IN DOMESTIC ANIMALS, Issue 3-4 2000
T Klonisch
Contents The placental expression of relaxin, a member of the insulin-like family, has been studied in the placenta in various species with different histological types of materno-fetal interdigitation and trophoblast invasiveness. Placental relaxin expression in these species showed some common features. Relaxin was present in placental areas of intense feto-maternal nutrition- and gas-exchange and high growth potential, implicating relaxin to be involved in placental metabolism and placental growth. Differentiation of trophoblast cells along various lineage pathways affected relaxin gene activity and an inverse expression pattern of relaxin and MHC class I molecules was observed in equine pseudostratified trophoblast cells. A fall in peripheral plasma concentrations of relaxin prior to abortion appears to indicate impaired materno-fetal interdigitation which results in insufficient placentation. [source]

Role of Natural Killer Cell Subsets in Cardiac Allograft Rejection

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2006
M. E. McNerney
To achieve donor-specific immune tolerance to allogeneic organ transplants, it is imperative to understand the cell types involved in acute allograft rejection. In wild-type mice, CD4+ T cells are necessary and sufficient for acute rejection of cardiac allografts. However, when T-cell responses are suboptimal, such as in mice treated with costimulation-targeting agents or in CD28-deficient mice, and perhaps in transplanted patients taking immunosuppressive drugs, the participation of other lymphocytes such as CD8+ T cells and NK1.1+ cells becomes apparent. We found that host NK but not NKT cells were required for cardiac rejection. Ly49G2+ NK cells suppressed rejection, whereas a subset of NK cells lacking inhibitory Ly49 receptors for donor MHC class I molecules was sufficient to promote rejection. Notably, rejection was independent of the activating receptors Ly49D and NKG2D. Finally, our experiments supported a mechanism by which NK cells promote expansion and effector function of alloreactive T cells. Thus, therapies aimed at specific subsets of NK cells may facilitate transplantation tolerance in settings of impaired T-cell function. [source]

Molecular characterization of major and minor MHC class I and II genes in B21-like haplotypes in chickens

ANIMAL GENETICS, Issue 4 2000
H R Juul-Madsen
The major histocompatibility complex (MHC) sequences of three B21-like haplotypes deriving from very different origins including the Red Jungle Fowl Gallus Gallus gallus were compared with the MHC sequences of the standard B21 haplotype from Scandinavian White Leghorn Gallus domesticus. The present analysis reveals two cDNA sequences for B - F and two cDNA sequences for B - LB for every B21-like haplotype, including B21 itself. Contrary to expectation, no sequence polymorphism in the antigen-binding domains of the MHC genes, between the investigated haplotypes, was found. The relative level of MHC class I molecules on the surface of leukocytes measured by flow cytometry was also analysed and found to be low in Marek's Disease (MD)-resistant B haplotypes (B21 and B21-like) and high in MD-susceptible B haplotypes (B15 and B19). However, in heterozygous (resistant/susceptible) animals, the relative level was almost as high as in susceptible haplotypes. [source]

Expression, purification, crystallization and preliminary X-ray diffraction analysis of rhesus macaque CD8,, homodimer

ACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 4 2010
Lili Zong
As a T-cell co-receptor, CD8 binds to MHC class I molecules and plays a pivotal role in the activation of cytotoxic T lymphocytes. To date, structures of CD8 have been solved for two different mammals: human and mouse. The infection of rhesus macaques (Macaca mulatta) by simian immunodeficiency virus (SIV) is the best animal model for studying HIV. In this study, the rhesus macaque CD8 (rCD8) ,, homodimer was obtained and rCD8, exodomain protein crystals were successfully obtained for further structural analysis. Diffraction data were collected to a resolution of 2.4,Å. The crystal belonged to space group P212121, with unit-cell parameters a = 46.52, b = 56.28, c = 82.40,Å. These data will facilitate further studies on the structural differences between these CD8 structures and the cellular immune responses of rhesus macaque. [source]

Killing tumor cells through their surface ,2 -microglobulin or major histocompatibility complex class I molecules

CANCER, Issue 7 2010
Jing Yang PhD
Abstract Targeted antibody-based therapy has been used successfully to treat cancers. Recent studies have demonstrated that tumor cells treated with antibodies specific for ,2 -microglobulin (,2M) or major histocompatibility complex (MHC) class I molecules undergo apoptosis in vitro and in vivo (mouse models). Antibodies against ,2M or MHC class I induce tumor cell apoptosis by 1) recruiting MHC class I molecules to lipid rafts and activating LYN kinase and the signal-transducing enzyme phospholipase C-,2-dependent c-Jun N-terminal kinase signaling pathway and 2) expelling interleukin 6 and insulin-like growth factor 1 receptors out of lipid rafts and inhibiting the growth and survival factor-induced activation of the phosphatidylinositol 3-kinase/Akt and extracellular signal-related kinase pathways. Consequently, mitochondrial integrity is compromised, and the caspase-9-dependent cascade is activated in treated tumor cells. However, although ,2M and MHC class I are expressed on normal hematopoietic cells, which is a potential safety concern, the monoclonal antibodies were selective to tumor cells and did not damage normal cells in vitro or in human-like mouse models. These findings suggest that targeting ,2M or MHC class I by using antibodies or other agents offers a potential therapeutic approach for ,2M/MHC class I-expressing malignancies. Cancer 2010. © 2010 American Cancer Society. [source]