scholarly journals Discovery of an ancient MHC category with both class I and class II features

2021 ◽  
Vol 118 (51) ◽  
pp. e2108104118
Author(s):  
Kazuhiko Okamura ◽  
Johannes M. Dijkstra ◽  
Kentaro Tsukamoto ◽  
Unni Grimholt ◽  
Geert F. Wiegertjes ◽  
...  
Keyword(s):  
Mhc Class I ◽  
Class Ii ◽  
Class I ◽  
Sequence Motifs ◽  
Critical Question ◽  
Specific Sequence ◽  
Mhc Molecules ◽  
Mhc Class I Molecule ◽  
Chain Organization ◽  
Lymphocyte Populations

Two classes of major histocompatibility complex (MHC) molecules, MHC class I and class II, play important roles in our immune system, presenting antigens to functionally distinct T lymphocyte populations. However, the origin of this essential MHC class divergence is poorly understood. Here, we discovered a category of MHC molecules (W-category) in the most primitive jawed vertebrates, cartilaginous fish, and also in bony fish and tetrapods. W-category, surprisingly, possesses class II–type α- and β-chain organization together with class I–specific sequence motifs for interdomain binding, and the W-category α2 domain shows unprecedented, phylogenetic similarity with β2-microglobulin of class I. Based on the results, we propose a model in which the ancestral MHC class I molecule evolved from class II–type W-category. The discovery of the ancient MHC group, W-category, sheds a light on the long-standing critical question of the MHC class divergence and suggests that class II type came first.

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

Immunosuppressive properties of CD95L-transduced “killer” hybrids created by fusing donor- and recipient-derived dendritic cells

Blood ◽  
2001 ◽  
Vol 98 (12) ◽  
pp. 3465-3472 ◽  
Author(s):  
Hiroyuki Matsue ◽  
Keiko Matsue ◽  
Masahiro Kusuhara ◽  
Tadashi Kumamoto ◽  
Ko Okumura ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Organ Transplantation ◽  
Mhc Class I ◽  
Hematopoietic Cell Transplantation ◽  
Class Ii ◽  
Class I ◽  
Delayed Type Hypersensitivity ◽  
Mhc Molecules ◽  
Dc Line

Abstract Allogeneic immune responses, which are initiated by dendritic cells (DCs) of both donor and host origins, remain a major obstacle in organ transplantation. Presentation of intact major histocompatibility complex (MHC) molecules by allogeneic DCs and allogeneic peptides by syngeneic DCs leads to complex allogeneic immune responses. This study reports a novel strategy designed to suppress both pathways. A stable DC line XS106 (A/J mouse origin) was transfected with CD95L cDNA and fused with splenic DCs purified from allogeneic BALB/c mice. The resulting “killer” DC-DC hybrids: (1) expressed CD95L and MHC class I and class II molecules of both A/J and BALB/c origins, while maintaining otherwise characteristic surface phenotypes of mature DCs; (2) inhibited MHC class I– and class II–restricted mixed leukocyte reactions between the parental strains by triggering apoptosis of alloreactive T cells; and (3) abolished delayed-type hypersensitivity responses of A/J (and BALB/c) mice to BALB/c-associated (and A/J-associated) alloantigens when injected intravenously into A/J (and BALB/c) mice. The onset of graft-versus-host disease in (BALB/c × A/J) F1 hosts receiving A/J-derived hematopoietic cell transplantation was suppressed significantly (P < .001) by killer DC-DC hybrid treatment. These results form both technical and conceptual frameworks for clinical applications of CD95L-transduced killer hybrids created between donor DCs and recipient DCs in the prevention of allogeneic immune responses following organ transplantation.

scholarly journals The Recognition of the Nonclassical Major Histocompatibility Complex (MHC) Class I Molecule, T10, by the γδ T Cell, G8

1997 ◽  
Vol 185 (7) ◽  
pp. 1223-1230 ◽  
Author(s):  
Michael P. Crowley ◽  
Ziv Reich ◽  
Nasim Mavaddat ◽  
John D. Altman ◽  
Yueh-hsiu Chien
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Mhc Class I ◽  
Class I ◽  
Γδ T Cell ◽  
Major Histocompatibility ◽  
Mhc Molecules ◽  
Histocompatibility Complex ◽  
Mhc Class I Molecule ◽  
T Cell Clone

Recent studies have shown that many nonclassical major histocompatibility complex (MHC) (class Ib) molecules have distinct antigen-binding capabilities, including the binding of nonpeptide moieties and the binding of peptides that are different from those bound to classical MHC molecules. Here, we show that one of the H-2T region–encoded molecules, T10, when produced in Escherichia coli, can be folded in vitro with β2-microglobulin (β2m) to form a stable heterodimer in the absence of peptide or nonpeptide moieties. This heterodimer can be recognized by specific antibodies and is stimulatory to the γδ T cell clone, G8. Circular dichroism analysis indicates that T10/β2m has structural features distinct from those of classical MHC class I molecules. These results suggest a new way for MHC-like molecules to adopt a peptide-free structure and to function in the immune system.

scholarly journals Restricted MHC–peptide repertoire predisposes to autoimmunity

2005 ◽  
Vol 202 (1) ◽  
pp. 73-84 ◽  
Author(s):  
Nadezda N. Logunova ◽  
Christophe Viret ◽  
Leonid A. Pobezinsky ◽  
Sara A. Miller ◽  
Dmitri B. Kazansky ◽  
...  
Keyword(s):  
Mhc Class I ◽  
Mhc Class Ii ◽  
Selective Advantage ◽  
Class Ii ◽  
Structural Features ◽  
Peptide Ligands ◽  
Class I ◽  
Class I Mhc ◽  
Mhc Molecules ◽  
Single Complex

MHC molecules associated with autoimmunity possess known structural features that limit the repertoire of peptides that they can present. Such limitation gives a selective advantage to TCRs that rely on interaction with the MHC itself, rather than with the peptide residues. At the same time, negative selection is impaired because of the lack of negatively selecting peptide ligands. The combination of these factors may predispose to autoimmunity. We found that mice with an MHC class II–peptide repertoire reduced to a single complex demonstrated various autoimmune reactions. Transgenic mice bearing a TCR (MM14.4) cloned from such a mouse developed severe autoimmune dermatitis. Although MM14.4 originated from a CD4+ T cell, dermatitis was mediated by CD8+ T cells. It was established that MM14.4+ is a highly promiscuous TCR with dual MHC class I/MHC class II restriction. Furthermore, mice with a limited MHC–peptide repertoire selected elevated numbers of TCRs with dual MHC class I/MHC class II restriction, a likely source of autoreactivity. Our findings may help to explain the link between MHC class I responses that are involved in major autoimmune diseases and the well-established genetic linkage of these diseases with MHC class II.

The Study of Specificities of Interaction between Peptides and MHC Molecules

2010 ◽  
Vol 143-144 ◽  
pp. 1254-1258 ◽  
Author(s):  
Tao Liu ◽  
Zhan Xin Zhang ◽  
Huan Wei ◽  
Hong Kui Hu ◽  
Feng Ming Wang
Keyword(s):  
Amino Acids ◽  
Mhc Class I ◽  
Class I ◽  
Support Vector ◽  
Binding Affinities ◽  
Mhc Molecules ◽  
Mhc Class I Molecule ◽  
Antigen Peptide ◽  
Amino Acid Descriptors ◽  
Epitope Vaccines

Determining which peptides bind to a specific major histocompatibility complex (MHC) class I molecule is not only helpful to understand the mechanism of immunity, but also to develop effective anti-tumor epitope vaccines. In order to further study the specificity of MHC class I molecule binding antigen peptide, the support vector regression (SVR) and four amino acid descriptors were used to build four models of predicting binding affinities between peptides and MHC class I molecules. Comparison among performances of the four models indicated that the model based on physicochemical properties of amino acids is more satisfying (AC=75.0%, CC=0.499). Furthermore, the specificities of MHC class I molecule binding antigen peptide were obtained through analysis based on the contribution of the amino acids to peptide-MHC class I molecule binding affinities in the predictive model.

Distribution of MHC class I and of MHC class II molecules in macrophages infected with Leishmania amazonensis

1994 ◽  
Vol 107 (1) ◽  
pp. 69-82 ◽  
Author(s):  
T. Lang ◽  
C. de Chastellier ◽  
C. Frehel ◽  
R. Hellio ◽  
P. Metezeau ◽  
...  
Keyword(s):  
Mhc Class I ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Class I ◽  
Mhc Molecules ◽  
Cd8 T Lymphocytes ◽  
Membrane Components ◽  
Endocytic Compartments ◽  
Mhc Class I Molecules ◽  
Mhc Class Ii Molecules

Macrophages, being apparently the only cells that in vivo allow the growth of the intracellular pathogen Leishmania, are likely candidates to present antigens to Leishmania-specific CD4+ and CD8+ T lymphocytes, known to be involved in the resolution or in the development of lesions induced by these parasites, and recognizing processed antigens bound to MHC class I and MHC class II molecules, respectively. In the present study, we analysed by confocal microscopy and by immunoelectron microscopy the subcellular distribution of both MHC class I and class II molecules in mouse (Balb/c and C57BL/6 strains) bone marrow-derived macrophages infected for 12 to 48 hours with Leishmania amazonensis amastigotes and activated with gamma interferon to determine the intracellular sites where Leishmania antigens and MHC molecules meet and can possibly interact. Double labelings with anti-MHC molecule antibodies and with either propidium iodide or an anti-amastigote antibody allowed localization of MHC molecules with regard to the endocytic compartments housing Leishmania amastigotes, organelles known as the parasitophorous vacuoles (PV) and which most likely contain the highest concentration of parasite antigens in the host cell. Both uninfected and infected macrophages from Balb/c mice expressed the MHC class I molecules H-2Kd and H-2Dd on their cell surface but no significant amount of these molecules could be detected in the PV, which indicates that, if infected macrophages play a role in the induction of Leishmania-specific CD8+ T lymphocytes, PV are probably not loading compartments for MHC class I molecules. In contrast, MHC class II molecules were found to be associated with the PV membranes as shown previously with microscopic techniques at lower resolution (Antoine et al. Infect. Immun. 59, 764–775, 1991). In addition, we show here that, 48 hours after infection of Balb/c macrophages, in about 90% of PV containing MHC class II molecules, the latter were mainly or solely localized at the attachment zone of amastigotes to PV membranes. This peculiar distribution, especially well demonstrated using confocal microscopy, was confirmed by subcellular fluorescence cytometry of infected macrophages stained for the MHC class II molecules. The following data agree with the idea that PV-associated MHC class II molecules establish specific interactions with plasma membrane components of amastigotes. First, the polarized localization of class II appeared specific to these molecules, since the distribution of the lysosomal glycoproteins Igp110 and Igp120, of the macrosialin (a macrophage-specific marker of endocytic compartments) and of the GTP-binding protein rab7p, shown here as being PV membrane components, was homogeneous.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals The Missing Link in Epstein-Barr Virus Immune Evasion: the BDLF3 Gene Induces Ubiquitination and Downregulation of Major Histocompatibility Complex Class I (MHC-I) and MHC-II

2015 ◽  
Vol 90 (1) ◽  
pp. 356-367 ◽  
Author(s):  
Laura L. Quinn ◽  
Luke R. Williams ◽  
Claire White ◽  
Calum Forrest ◽  
Jianmin Zuo ◽  
...  
Keyword(s):  
T Cell ◽  
Mhc Class I ◽  
Immune Evasion ◽  
Class Ii ◽  
Lytic Cycle ◽  
Class I ◽  
Target Cells ◽  
Cell Recognition ◽  
T Cell Recognition ◽  
Mhc Molecules

ABSTRACTThe ability of Epstein-Barr virus (EBV) to spread and persist in human populations relies on a balance between host immune responses and EBV immune evasion. CD8+cells specific for EBV late lytic cycle antigens show poor recognition of target cells compared to immediate early and early antigen-specific CD8+cells. This phenomenon is due in part to the early EBV protein BILF1, whose immunosuppressive activity increases with lytic cycle progression. However, published data suggest the existence of a hitherto unidentified immune evasion protein further enhancing protection against late EBV antigen-specific CD8+cells. We have now identified the late lytic BDLF3 gene as the missing link accounting for efficient evasion during the late lytic cycle. Interestingly, BDLF3 also contributes to evasion of CD4+cell responses to EBV. We report that BDLF3 downregulates expression of surface major histocompatibility complex (MHC) class I and class II molecules in the absence of any effect upon other surface molecules screened, including CD54 (ICAM-1) and CD71 (transferrin receptor). BDLF3 both enhanced internalization of surface MHC molecules and reduced the rate of their appearance at the cell surface. The reduced expression of surface MHC molecules correlated with functional protection against CD8+and CD4+T cell recognition. The molecular mechanism was identified as BDLF3-induced ubiquitination of MHC molecules and their subsequent downregulation in a proteasome-dependent manner.IMPORTANCEImmune evasion is a necessary feature of viruses that establish lifelong persistent infections in the face of strong immune responses. EBV is an important human pathogen whose immune evasion mechanisms are only partly understood. Of the EBV immune evasion mechanisms identified to date, none could explain why CD8+T cell responses to late lytic cycle genes are so infrequent and, when present, recognize lytically infected target cells so poorly relative to CD8+T cells specific for early lytic cycle antigens. The present work identifies an additional immune evasion protein, BDLF3, that is expressed late in the lytic cycle and impairs CD8+T cell recognition by targeting cell surface MHC class I molecules for ubiquitination and proteasome-dependent downregulation. Interestingly, BDLF3 also targets MHC class II molecules to impair CD4+T cell recognition. BDLF3 is therefore a rare example of a viral protein that impairs both the MHC class I and class II antigen-presenting pathways.

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.

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