scholarly journals Presentation of Exogenous Antigens on Major Histocompatibility Complex (MHC) Class I and MHC Class II Molecules Is Differentially Regulated during Dendritic Cell Maturation

2003 ◽  
Vol 198 (1) ◽  
pp. 111-122 ◽  
Author(s):  
Lélia Delamarre ◽  
Hilda Holcombe ◽  
Ira Mellman
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class Ii ◽  
Dendritic Cell Maturation ◽  
Mouse Bone Marrow ◽  
Major Histocompatibility ◽  
Cd40 Ligation ◽  
Mhc I ◽  
Cross Presentation ◽  
Mhc Ii ◽  
Histocompatibility Complex

During maturation, dendritic cells (DCs) regulate their capacity to process and present major histocompatibility complex (MHC) II–restricted antigens. Here we show that presentation of exogenous antigens by MHC I is also subject to developmental control, but in a fashion strikingly distinct from MHC II. Immature mouse bone marrow–derived DCs internalize soluble ovalbumin and sequester the antigen intracellularly until they receive an appropriate signal that induces cross presentation. At that time, peptides are generated in a proteasome-dependent fashion and used to form peptide–MHC I complexes that appear at the plasma membrane. Unlike MHC II, these events do not involve a marked redistribution of preexisting MHC I molecules from intracellular compartments to the DC surface. Moreover, out of nine stimuli well known to induce the phenotypic maturation of DCs and to promote MHC II presentation, only two (CD40 ligation, disruption of cell–cell contacts) activated cross presentation on MHC I. In contrast, formation of peptide–MHC I complexes from endogenous cytosolic antigens occurs even in unstimulated, immature DCs. Thus, the MHC I and MHC II pathways of antigen presentation are differentially regulated during DC maturation.

scholarly journals CD1 and Major Histocompatibility Complex II Molecules Follow a Different Course during Dendritic Cell Maturation

2003 ◽  
Vol 14 (8) ◽  
pp. 3378-3388 ◽  
Author(s):  
Nicole N. van der Wel ◽  
Masahiko Sugita ◽  
Donna M. Fluitsma ◽  
Xaiochun Cao ◽  
Gerty Schreibelt ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Major Histocompatibility Complex ◽  
Dendritic Cell ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Dendritic Cell Maturation ◽  
Cell Maturation ◽  
Major Histocompatibility ◽  
Mhc Molecules ◽  
Histocompatibility Complex

The maturation of dendritic cells is accompanied by the redistribution of major histocompatibility complex (MHC) class II molecules from the lysosomal MHC class II compartment to the plasma membrane to mediate presentation of peptide antigens. Besides MHC molecules, dendritic cells also express CD1 molecules that mediate presentation of lipid antigens. Herein, we show that in human monocyte-derived dendritic cells, unlike MHC class II, the steady-state distribution of lysosomal CD1b and CD1c isoforms was unperturbed in response to lipopolysaccharide-induced maturation. However, the lysosomes in these cells underwent a dramatic reorganization into electron dense tubules with altered lysosomal protein composition. These structures matured into novel and morphologically unique compartments, here termed mature dendritic cell lysosomes (MDL). Furthermore, we show that upon activation mature dendritic cells do not lose their ability of efficient clathrin-mediated endocytosis as demonstrated for CD1b and transferrin receptor molecules. Thus, the constitutive endocytosis of CD1b molecules and the differential sorting of MHC class II from lysosomes separate peptide- and lipid antigen-presenting molecules during dendritic cell maturation.

scholarly journals MPYS, a Novel Membrane Tetraspanner, Is Associated with Major Histocompatibility Complex Class II and Mediates Transduction of Apoptotic Signals

2008 ◽  
Vol 28 (16) ◽  
pp. 5014-5026 ◽  
Author(s):  
Lei Jin ◽  
Paul M. Waterman ◽  
Karen R. Jonscher ◽  
Cindy M. Short ◽  
Nichole A. Reisdorph ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class Ii ◽  
Cell Activation ◽  
Cytoplasmic Tail ◽  
Class Ii ◽  
Antigenic Peptides ◽  
Major Histocompatibility ◽  
Mhc Ii ◽  
Histocompatibility Complex ◽  
Death Signals

ABSTRACT Although the best-defined function of type II major histocompatibility complex (MHC-II) is presentation of antigenic peptides to T lymphocytes, these molecules can also transduce signals leading alternatively to cell activation or apoptotic death. MHC-II is a heterodimer of two transmembrane proteins, each containing a short cytoplasmic tail that is dispensable for transduction of death signals. This suggests the function of an undefined MHC-II-associated transducer in signaling the death response. Here we describe a novel plasma membrane tetraspanner (MPYS) that is associated with MHC-II and mediates its transduction of death signals. MPYS is unusual among tetraspanners in containing an extended C-terminal cytoplasmic tail (∼140 amino acids) with multiple embedded signaling motifs. MPYS is tyrosine phosphorylated upon MHC-II aggregation and associates with inositol lipid and tyrosine phosphatases. Finally, MHC class II-mediated cell death signaling requires MPYS-dependent activation of the extracellular signal-regulated kinase signaling pathway.

scholarly journals Processing of Mycobacterium tuberculosis Antigen 85B Involves Intraphagosomal Formation of Peptide–Major Histocompatibility Complex II Complexes and Is Inhibited by Live Bacilli that Decrease Phagosome Maturation

2001 ◽  
Vol 194 (10) ◽  
pp. 1421-1432 ◽  
Author(s):  
Lakshmi Ramachandra ◽  
Erika Noss ◽  
W. Henry Boom ◽  
Clifford V. Harding
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Major Histocompatibility Complex ◽  
Mhc Class Ii ◽  
Immune Surveillance ◽  
Interferon Γ ◽  
Hybridoma Cells ◽  
Phagosome Maturation ◽  
Major Histocompatibility ◽  
Mhc Ii ◽  
Histocompatibility Complex

Mycobacterium tuberculosis (MTB) inhibits phagosomal maturation to promote its survival inside macrophages. Control of MTB infection requires CD4 T cell responses and major histocompatibility complex (MHC) class II (MHC-II) processing of MTB antigens (Ags). To investigate phagosomal processing of MTB Ags, phagosomes containing heat-killed (HK) or live MTB were purified from interferon-γ (IFN-γ)–activated macrophages by differential centrifugation and Percoll density gradient subcellular fractionation. Flow organellometry and Western blot analysis showed that MTB phagosomes acquired lysosome-associated membrane protein-1 (LAMP-1), MHC-II, and H2-DM. T hybridoma cells were used to detect MTB Ag 85B(241–256)–I-Ab complexes in isolated phagosomes and other subcellular fractions. These complexes appeared initially (within 20 min) in phagosomes and subsequently (>20 min) on the plasma membrane, but never within late endocytic compartments. Macrophages processed HK MTB more rapidly and efficiently than live MTB; phagosomes containing live MTB expressed fewer Ag 85B(241–256)–I-Ab complexes than phagosomes containing HK MTB. This is the first study of bacterial Ag processing to directly show that peptide–MHC-II complexes are formed within phagosomes and not after export of bacterial Ags from phagosomes to endocytic Ag processing compartments. Live MTB can alter phagosome maturation and decrease MHC-II Ag processing, providing a mechanism for MTB to evade immune surveillance and enhance its survival within the host.

scholarly journals Major histocompatibility complex in Osteichthyes

2020 ◽  
Vol 64 (1) ◽  
pp. 127-136
Author(s):  
Michał Stosik ◽  
Beata Tokarz-Deptuła ◽  
Wiesław Deptuła
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class I ◽  
Class I ◽  
Major Histocompatibility ◽  
Mhc I ◽  
Spotted Gar ◽  
Mhc Ii ◽  
Histocompatibility Complex ◽  
Lepisosteus Oculatus ◽  
Mhc Class I Molecules

AbstractBased on analysis of available genome sequences, five gene lineages of MHC class I molecules (MHC I-U, -Z, -S, -L and -P) and one gene lineage of MHC class II molecules (MHC II-D) have been identified in Osteichthyes. In the latter lineage, three MHC II molecule sublineages have been identified (MHC II-A, -B and -E). As regards MHC class I molecules in Osteichthyes, it is important to take note of the fact that the lineages U and Z in MHC I genes have been identified in almost all fish species examined so far. Phylogenetic studies into MHC II molecule genes of sublineages A and B suggest that they may be descended from the genes of the sublineage named A/B that have been identified in spotted gar (Lepisosteus oculatus). The sublineage E genes of MHC II molecules, which represent the group of non-polymorphic genes with poor expression in the tissues connected with the immune system, are present in primitive fish, i.e. in paddlefish, sturgeons and spotted gar (Lepisosteus oculatus), as well as in cyprinids (Cyprinidae), Atlantic salmon (Salmo salar), and rainbow trout (Oncorhynchus mykiss). Full elucidation of the details relating to the organisation and functioning of the particular components of the major histocompatibility complex in Osteichthyes can advance the understanding of the evolution of the MHC molecule genes and the immune mechanism.

scholarly journals Major histocompatibility complex selection dynamics in pathogen-infected túngara frog ( Physalaemus pustulosus ) populations

2016 ◽  
Vol 12 (8) ◽  
pp. 20160345 ◽  
Author(s):  
Tiffany A. Kosch ◽  
Arnaud Bataille ◽  
Chelsea Didinger ◽  
John A. Eimes ◽  
Sofia Rodríguez-Brenes ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Major Histocompatibility Complex ◽  
Mhc Class Ii ◽  
Balancing Selection ◽  
Directional Selection ◽  
Major Histocompatibility ◽  
Physalaemus Pustulosus ◽  
Mhc Ii ◽  
Histocompatibility Complex ◽  
Selection Dynamics

Pathogen-driven selection can favour major histocompatibility complex (MHC) alleles that confer immunological resistance to specific diseases. However, strong directional selection should deplete genetic variation necessary for robust immune function in the absence of balancing selection or challenges presented by other pathogens. We examined selection dynamics at one MHC class II (MHC-II) locus across Panamanian populations of the túngara frog, Physalaemus pustulosus , infected by the amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd). We compared MHC-II diversity in highland túngara frog populations, where amphibian communities have experienced declines owing to Bd, with those in the lowland region that have shown no evidence of decline. Highland region frogs had MHC variants that confer resistance to Bd. Variant fixation appeared to occur by directional selection rather than inbreeding, as overall genetic variation persisted in populations. In Bd-infected lowland sites, however, selective advantage may accrue to individuals with only one Bd-resistance allele, which were more frequent. Environmental conditions in lowlands should be less favourable for Bd infection, which may reduce selection for specific Bd resistance in hosts. Our results suggest that MHC selection dynamics fluctuate in túngara frog populations as a function of the favourability of habitat to pathogen spread and the vulnerability of hosts to infection.

Cellular and Gene Therapy for Major Histocompatibility Complex Class II Deficiency

Physiology ◽  
2004 ◽  
Vol 19 (3) ◽  
pp. 154-158 ◽  
Author(s):  
Franck Matheux ◽  
Jean Villard
Keyword(s):  
Gene Therapy ◽  
Major Histocompatibility Complex ◽  
Mouse Model ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Mhc Ii ◽  
Histocompatibility Complex ◽  
Mhc Class Ii Deficiency

Major histocompatibility complex (MHC) class II deficiency is a primary immunodeficiency. Lentiviral vectors are used for gene therapy in a mouse model of this disease. In addition, by a direct genetic correction approach, a diagnostic test to determine which of the four MHC II genes is defective in new MHC II-deficiency patients has been optimized.

scholarly journals CTCF Controls Expression and Chromatin Architecture of the Human Major Histocompatibility Complex Class II Locus

2010 ◽  
Vol 30 (17) ◽  
pp. 4211-4223 ◽  
Author(s):  
Parimal Majumder ◽  
Jeremy M. Boss
Keyword(s):  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Mhc Class Ii ◽  
Gene Promoter ◽  
Class Ii ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Human Major Histocompatibility Complex ◽  
Mhc Ii ◽  
Histocompatibility Complex

ABSTRACT The major histocompatibility complex class II (MHC-II) locus includes a dense cluster of genes that function to initiate immune responses. Expression of insulator CCCTC binding factor (CTCF) was found to be required for expression of all MHC class II genes associated with antigen presentation. Ten CTCF sites that divide the MHC-II locus into apparent evolutionary domains were identified. To define the role of CTCF in mediating regulation of the MHC II genes, chromatin conformation capture assays, which provide an architectural assessment of a locus, were conducted across the MHC-II region. Depending on whether MHC-II genes and the class II transactivator (CIITA) were being expressed, two CTCF-dependent chromatin architectural states, each with multiple configurations and interactions, were observed. These states included the ability to express MHC-II gene promoter regions to interact with nearby CTCF sites and CTCF sites to interact with each other. Thus, CTCF organizes the MHC-II locus into a novel basal architecture of interacting foci and loop structures that rearranges in the presence of CIITA. Disruption of the rearranged states eradicated expression, suggesting that the formation of these structures is key to coregulation of MHC-II genes and the locus.

scholarly journals The Contribution of Major Histocompatibility Complex Class II Genes to an Association with Autoimmune Diseases

Acta Naturae ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 4-12 ◽  
Author(s):  
M. Yu. Zakharova ◽  
T. A. Belyanina ◽  
A. V. Sokolov ◽  
I. S. Kiselev ◽  
A. E. Mamedov
Keyword(s):  
Major Histocompatibility Complex ◽  
Autoimmune Diseases ◽  
Mhc Class Ii ◽  
Lupus Erythematosus ◽  
Class Ii ◽  
Major Histocompatibility ◽  
Genetic Studies ◽  
Mhc Ii ◽  
Histocompatibility Complex

Genetic studies of patients with autoimmune diseases have shown that one of the most important roles in the developing of these diseases is played by a cluster of genes of the major histocompatibility complex (MHC), as compared with other genome areas. Information on the specific contribution of MHC alleles, mostly MHC class II ones, to the genetic predisposition to autoimmune diseases is crucial for understanding their pathogenesis. This review dwells on the most relevant aspects of this problem: namely, the correlation between carriage of certain MHC II alleles and an increased (positively associated allele) or reduced (negatively associated allele) probability of developing the most common autoimmune diseases, such as type 1 diabetes, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, autoimmune thyroiditis, etc. The most universal haplotypes, DR3-DQ2 and DR4-DQ8, are positively associated with many of these diseases, while the universal allele HLA-DRB1*0701 is protective.

scholarly journals Antigen cross-presentation by macrophages

2021 ◽  
pp. 14-23
Author(s):  
И.Ю. Малышев ◽  
Л.В. Кузнецова ◽  
О.О. Чернышова ◽  
О.П. Буданова ◽  
Л.Ю. Бахтина
Keyword(s):  
Major Histocompatibility Complex ◽  
Peritoneal Macrophages ◽  
Tissue Type ◽  
Major Histocompatibility ◽  
Blood Monocytes ◽  
Mhc I ◽  
Cross Presentation ◽  
Histocompatibility Complex ◽  
Antigen Transfer ◽  
The Cross

В обзоре рассматриваются механизмы кросс-презентации антигена и особенности этого процесса в макрофагах. Представлено сравнение особенностей кросс-презентации в дендритных клетках и разных фенотипах макрофагов. Описаны пути кросс-презентации -протеасомный и вакуолярный. Протеасомный путь состоит из следующих стадий: 1) захват антигена в фагосому; 2) сохранение антигена в фагосоме; 3) перенос антигена в цитозоль и его расщепление в протеасоме до олигопептидов; 4) перенос олигопептидов в компартменты, содержащие главный комплекс гистосовместимости I типа (major histocompatibility complex I, MHC I); 5) загрузка олигопептида на MHC-I и перенос на поверхность клетки. Вакуолярный путь начинается сходно с протеасомным, но отличается в том, что захваченный антиген не покидает фагосому, а там же расщепляется и нагружается на MHC-I. Макрофаги могут использовать любой из этих путей. Макрофаги, происходящие из моноцитов крови, используют вакуолярный путь, макрофаги красной пульпы селезенки - протеасомный, а перитонеальные - и тот, и другой. Эффективность кросс-презентации макрофагов зависит от его тканевого типа. При разработке методов иммунотерапии, основанной на макрофагах, важно понимать стадии обоих путей кросс-презентации, поскольку каждая из них может рассматриваться как мишень для повышения эффективности кросс-презентации антигена и соответственно, эффективности иммунотерапии рака. This review focuses on mechanisms of antigen cross-presentation and features of this process in macrophages. Features of the cross-presentation in dendritic cells and in various macrophage phenotypes are compared. The cross-presentation can be the result of either the proteasomal or vacuolar pathway. The proteasomal pathway includes the following stages: 1) antigen capture into the phagosome; 2) antigen preservation in the phagosome; 3) antigen transfer to the cytosol and its cleavage in the proteasome to oligopeptides; 4) oligopeptide transfer into major histocompatibility complex (MHC) I-containing compartments; 5) oligopeptide loading onto the MHC I and transferring it to the cell surface. The vacuolar pathway begins in a similar way as the proteasomal pathway but differs in that the captured antigen does not leave the phagosome, but is cleaved there and loaded onto MHC I. Macrophages can use any of these pathways. Macrophages originating from blood monocytes use the vacuolar pathway; macrophages of the red pulp of the spleen use the proteasomal pathway, and peritoneal macrophages use both. The effectiveness of cross-presentation of macrophages depends on the macrophage tissue type. When developing macrophage-based methods of immunotherapy, it is important to understand the stages of both cross-presentation pathways since each of them can be considered as a target for increasing the efficiency of antigen cross-presentation and, accordingly, the effectiveness of cancer immunotherapy.

scholarly journals Curli, Fibrous Surface Proteins ofEscherichia coli, Interact with Major Histocompatibility Complex Class I Molecules

1998 ◽  
Vol 66 (3) ◽  
pp. 944-949 ◽  
Author(s):  
Arne Olsén ◽  
Mary Jo Wick ◽  
Matthias Mörgelin ◽  
Lars Björck
Keyword(s):  
Major Histocompatibility Complex ◽  
Major Histocompatibility Complex Class ◽  
Cell Line ◽  
Class I ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Mhc I ◽  
E Coli ◽  
Mhc Ii ◽  
Histocompatibility Complex

ABSTRACT Curli are thin, coiled fibers expressed on the surface ofEscherichia coli that bind several matrix and plasma proteins such as fibronectin, laminin, plasminogen, tissue plasminogen activator, and H-kininogen. In this work, we examined the interactions between curli-expressing E. coli and human major histocompatibility complex class I (MHC-I) and class II (MHC-II) molecules. Curliated E. coli was found to interact with an MHC-I-expressing lymphoma cell line as shown by scanning electron microscopy, whereas the binding to a mutant variant of this cell line expressing small amounts of MHC-I molecules was significantly lower. Moreover, curli-expressing E. coli bound purified radiolabeled MHC-I but not MHC-II molecules, whereas an isogenic curli-deficient mutant strain showed no affinity for either MHC-I or MHC-II. Purified insoluble curli could also bind125I-labeled MHC-I molecules, and in Western blot experiments the 15-kDa curlin subunit protein bound intact MHC-I molecules as well as β2-microglobulin, the light chain of MHC-I molecules. A direct interaction between monomeric MHC-I molecules and a bacterial surface protein has previously not been reported. The binding of curli to MHC-I molecules, which are present on virtually all cells in higher vertebrates, will provide curliated E. coliwith ample opportunities to interact with a great variety of hosts and host cells. This should facilitate the adaptation of E. coli to different ecological niches, and in human infections the interaction between curli and MHC-I molecules could contribute to adherence and colonization.

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