scholarly journals The Crystal Structure of the MHC Class I (MHC-I) Molecule in the Green Anole Lizard Demonstrates the Unique MHC-I System in Reptiles

2021 ◽  
Vol 206 (7) ◽  
pp. 1653-1667
Author(s):  
Yawen Wang ◽  
Zehui Qu ◽  
Lizhen Ma ◽  
Xiaohui Wei ◽  
Nianzhi Zhang ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Mhc Class I ◽  
Class I ◽  
Class I Mhc ◽  
Mhc I ◽  
Anole Lizard ◽  
Green Anole ◽  
Green Anole Lizard

Ligand Design for Specific MHC Class I Molecules on the Cell Surface

2020 ◽  
Author(s):  
Xizheng Sun ◽  
Reika Tokunaga ◽  
Yoko Nagai ◽  
Ryo Miyahara ◽  
Akihiro Kishimura ◽  
...  
Keyword(s):  
Cell Surface ◽  
Mhc Class I ◽  
Targeted Delivery ◽  
Peptide Ligands ◽  
Class I ◽  
Class I Mhc ◽  
Mhc I ◽  
Histocompatibility Complex ◽  
High Binding Affinity ◽  
Mhc Class I Molecules

<p><a></a><a></a><a>We have validated that ligand peptides designed from antigen peptides could be used for targeting specific major histocompatibility complex class I (MHC-I)</a> molecules on cell surface. To design the ligand peptides, we used reported antigen peptides for each MHC-I molecule with high binding affinity. From the crystal structure of the peptide/MHC-I complexes, we determined a modifiable residue in the antigen peptides and replaced this residue with a lysine with an ε-amine group modified with functional molecules. The designed ligand peptides successfully bound to cells expressing the corresponding MHC-I molecules via exchange of peptides bound to the MHC-I. We demonstrated that the peptide ligands could be used to transport a protein or a liposome to cells expressing the corresponding MHC-I. The present strategy may be useful for targeted delivery to cells overexpressing MHC-I, which have been observed autoimmune diseases.</p>

scholarly journals Immunoreceptor tyrosine-based inhibitory motif–dependent functions of an MHC class I-specific NK cell receptor

2017 ◽  
Vol 114 (40) ◽  
pp. E8440-E8447 ◽  
Author(s):  
Michael D. Bern ◽  
Diana L. Beckman ◽  
Takashi Ebihara ◽  
Samantha M. Taffner ◽  
Jennifer Poursine-Laurent ◽  
...  
Keyword(s):  
Nk Cells ◽  
Mhc Class I ◽  
Nk Cell ◽  
Single Gene ◽  
Cell Receptor ◽  
Class I ◽  
Class I Mhc ◽  
Mhc I ◽  
Receptor Repertoire

Natural killer (NK) cells express MHC class I (MHC-I)-specific receptors, such as Ly49A, that inhibit killing of cells expressing self–MHC-I. Self–MHC-I also “licenses” NK cells to become responsive to activating stimuli and regulates the surface level of NK-cell inhibitory receptors. However, the mechanisms of action resulting from these interactions of the Ly49s with their MHC-I ligands, particularly in vivo, have been controversial. Definitive studies could be derived from mice with targeted mutations in inhibitory Ly49s, but there are inherent challenges in specifically altering a single gene within a multigene family. Herein, we generated a knock-in mouse with a targeted mutation in the immunoreceptor tyrosine-based inhibitory motif (ITIM) of Ly49A that abolished the inhibitory function of Ly49A in cytotoxicity assays. This mutant Ly49A caused a licensing defect in NK cells, but the surface expression of Ly49A was unaltered. Moreover, NK cells that expressed this mutant Ly49A exhibited an altered inhibitory receptor repertoire. These results demonstrate that Ly49A ITIM signaling is critical for NK-cell effector inhibition, licensing, and receptor repertoire development.

scholarly journals Open MHC Class I Conformers: A Look through the Looking Glass

2021 ◽  
Vol 22 (18) ◽  
pp. 9738
Author(s):  
Fernando A. Arosa ◽  
André J. Esgalhado ◽  
Débora Reste-Ferreira ◽  
Elsa M. Cardoso
Keyword(s):  
Mhc Class I ◽  
Neuronal Development ◽  
Cell Communication ◽  
Fine Tuning ◽  
Class I ◽  
Tumor Escape ◽  
Class I Mhc ◽  
Mhc I ◽  
Surface Receptors ◽  
Extracellular Milieu

Studies carried out during the last few decades have consistently shown that cell surface MHC class I (MHC-I) molecules are endowed with functions unrelated with antigen presentation. These include cis–trans-interactions with inhibitory and activating KIR and LILR, and cis-interactions with receptors for hormones, growth factors, cytokines, and neurotransmitters. The mounting body of evidence indicates that these non-immunological MHC-I functions impact clinical and biomedical settings, including autoimmune responses, tumor escape, transplantation, and neuronal development. Notably, most of these functions appear to rely on the presence in hematopoietic and non-hematopoietic cells of heavy chains not associated with β2m and the peptide at the plasma membrane; these are known as open MHC-I conformers. Nowadays, open conformers are viewed as functional cis-trans structures capable of establishing physical associations with themselves, with other surface receptors, and being shed into the extracellular milieu. We review past and recent developments, strengthening the view that open conformers are multifunctional structures capable of fine-tuning cell signaling, growth, differentiation, and cell communication.

scholarly journals Self MHC class I–licensed NK cells enhance adaptive CD8 T-cell viral immunity

Blood ◽  
2011 ◽  
Vol 117 (19) ◽  
pp. 5133-5141 ◽  
Author(s):  
Michael D. Stadnisky ◽  
Xuefang Xie ◽  
Ebony R. Coats ◽  
Timothy N. Bullock ◽  
Michael G. Brown
Keyword(s):  
T Cells ◽  
T Cell ◽  
Nk Cells ◽  
Mhc Class I ◽  
Cd8 T Cells ◽  
Cd8 T Cell ◽  
Class I ◽  
Inhibitory Receptor ◽  
Class I Mhc ◽  
Mhc I

AbstractMHC class I (MHC I) is essential to NK- and T-cell effector and surveillance functions. However, it is unknown whether MHC I polymorphism influences adaptive immunity through NK cells. Previously, we found that MHC I Dk, a cognate ligand for the Ly49G2 inhibitory receptor, was essential to NK control of murine (M)CMV infection. Here we assessed the significance of NK inhibitory receptor recognition of MCMV on CD8 T cells in genetically defined MHC I Dk disparate mice. We observed that Dk-licensed Ly49G2+ NK cells stabilized and then enhanced conventional dendritic cells (cDCs) recovery after infection. Furthermore, licensed NK support of cDC recovery was essential to enhance the tempo, magnitude, and effector activity of virus-specific CD8 T cells. Minimal cDC and CD8 T-cell number differences after low-dose MCMV in Dk disparate animals further implied that licensed NK recognition of MCMV imparted qualitative cDC changes to enhance CD8 T-cell priming.

scholarly journals Emerging Roles of MHC Class I Region-Encoded E3 Ubiquitin Ligases in Innate Immunity

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiuzhi Jia ◽  
Chunyuan Zhao ◽  
Wei Zhao
Keyword(s):  
Innate Immunity ◽  
Mhc Class I ◽  
Ring Finger ◽  
Ubiquitin Ligases ◽  
Class I ◽  
E3 Ubiquitin Ligases ◽  
Innate Immune Responses ◽  
Class I Mhc ◽  
Mhc I ◽  
Histocompatibility Complex

The major histocompatibility complex (MHC) class I (MHC-I) region contains a multitude of genes relevant to immune response. Multiple E3 ubiquitin ligase genes, including tripartite motif 10 (TRIM10), TRIM15, TRIM26, TRIM27, TRIM31, TRIM38, TRIM39, TRIM40, and RING finger protein 39 (RNF39), are organized in a tight cluster, and an additional two TRIM genes (namely TRIM38 and TRIM27) telomeric of the cluster within the MHC-I region. The E3 ubiquitin ligases encoded by these genes possess important roles in controlling the intensity of innate immune responses. In this review, we discuss the E3 ubiquitin ligases encoded within the MHC-I region, highlight their regulatory roles in innate immunity, and outline their potential functions in infection, inflammatory and autoimmune diseases.

Increased hepatic iron in mice lacking classical MHC class I molecules

Blood ◽  
2002 ◽  
Vol 100 (12) ◽  
pp. 4239-4241 ◽  
Author(s):  
Elsa M. Cardoso ◽  
Maria G. Macedo ◽  
Pierre Rohrlich ◽  
Eduarda Ribeiro ◽  
Manuel T. Silva ◽  
...  
Keyword(s):  
Mhc Class I ◽  
Hereditary Hemochromatosis ◽  
Iron Accumulation ◽  
Class I ◽  
Hepatic Iron ◽  
Class I Mhc ◽  
Mhc I ◽  
Cd8 Cells ◽  
Histocompatibility Complex ◽  
First Time

Iron accumulation in the liver in hereditary hemochromatosis (HH) has been shown to be highly variable. Some studies point to the importance of major histocompatibility complex (MHC) class I (MHC-I) and CD8+ cells as modifiers of iron overload. In this report, using mice knockout for H2Kb−/−and H2Db−/− genes, it is demonstrated that lack of classical MHC-I molecules results in a spontaneous increase of nonheme iron content in the liver (mainly located in the hepatocytes) when compared to wild-type mice. In CD8−/−and Rag2−/− mice, no spontaneous hepatic iron accumulation was observed. These results demonstrate for the first time that classical MHC-I molecules could be involved in the regulation of iron metabolism and contribute to the established genotype/phenotype discrepancies seen in HH.

Ligand Design for Specific MHC Class I Molecules on the Cell Surface

2020 ◽  
Author(s):  
Xizheng Sun ◽  
Reika Tokunaga ◽  
Yoko Nagai ◽  
Ryo Miyahara ◽  
Akihiro Kishimura ◽  
...  
Keyword(s):  
Cell Surface ◽  
Mhc Class I ◽  
Targeted Delivery ◽  
Peptide Ligands ◽  
Class I ◽  
Class I Mhc ◽  
Mhc I ◽  
Histocompatibility Complex ◽  
High Binding Affinity ◽  
Mhc Class I Molecules

<p><a></a><a></a><a>We have validated that ligand peptides designed from antigen peptides could be used for targeting specific major histocompatibility complex class I (MHC-I)</a> molecules on cell surface. To design the ligand peptides, we used reported antigen peptides for each MHC-I molecule with high binding affinity. From the crystal structure of the peptide/MHC-I complexes, we determined a modifiable residue in the antigen peptides and replaced this residue with a lysine with an ε-amine group modified with functional molecules. The designed ligand peptides successfully bound to cells expressing the corresponding MHC-I molecules via exchange of peptides bound to the MHC-I. We demonstrated that the peptide ligands could be used to transport a protein or a liposome to cells expressing the corresponding MHC-I. The present strategy may be useful for targeted delivery to cells overexpressing MHC-I, which have been observed autoimmune diseases.</p>

scholarly journals The MHC Class-I Transactivator NLRC5: Implications to Cancer Immunology and Potential Applications to Cancer Immunotherapy

2021 ◽  
Vol 22 (4) ◽  
pp. 1964
Author(s):  
Akhil Shukla ◽  
Maryse Cloutier ◽  
Madanraj Appiya Santharam ◽  
Sheela Ramanathan ◽  
Subburaj Ilangumaran
Keyword(s):  
Cancer Immunotherapy ◽  
Mhc Class I ◽  
Antigen Processing ◽  
Immune Surveillance ◽  
Class I ◽  
Antigenic Peptides ◽  
Class I Mhc ◽  
Mhc I ◽  
Potential Applications ◽  
Antigen Processing And Presentation

The immune system constantly monitors the emergence of cancerous cells and eliminates them. CD8+ cytotoxic T lymphocytes (CTLs), which kill tumor cells and provide antitumor immunity, select their targets by recognizing tumor antigenic peptides presented by MHC class-I (MHC-I) molecules. Cancer cells circumvent immune surveillance using diverse strategies. A key mechanism of cancer immune evasion is downregulation of MHC-I and key proteins of the antigen processing and presentation machinery (APM). Even though impaired MHC-I expression in cancers is well-known, reversing the MHC-I defects remains the least advanced area of tumor immunology. The discoveries that NLRC5 is the key transcriptional activator of MHC-I and APM genes, and genetic lesions and epigenetic modifications of NLRC5 are the most common cause of MHC-I defects in cancers, have raised the hopes for restoring MHC-I expression. Here, we provide an overview of cancer immunity mediated by CD8+ T cells and the functions of NLRC5 in MHC-I antigen presentation pathways. We describe the impressive advances made in understanding the regulation of NLRC5 expression, the data supporting the antitumor functions of NLRC5 and a few reports that argue for a pro-tumorigenic role. Finally, we explore the possible avenues of exploiting NLRC5 for cancer immunotherapy.

scholarly journals A flexible MHC class I multimer loading system for large-scale detection of antigen-specific T cells

2018 ◽  
Vol 215 (5) ◽  
pp. 1493-1504 ◽  
Author(s):  
Jolien J. Luimstra ◽  
Malgorzata A. Garstka ◽  
Marthe C.J. Roex ◽  
Anke Redeker ◽  
George M.C. Janssen ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mhc Class I ◽  
Large Scale ◽  
Time Frame ◽  
Class I ◽  
Cell Transplant ◽  
Class I Mhc ◽  
Mhc I ◽  
Isolation And Characterization

Adaptive immunity is initiated by T cell recognition of specific antigens presented by major histocompatibility complexes (MHCs). MHC multimer technology has been developed for the detection, isolation, and characterization of T cells in infection, autoimmunity, and cancer. Here, we present a simple, fast, flexible, and efficient method to generate many different MHC class I (MHC I) multimers in parallel using temperature-mediated peptide exchange. We designed conditional peptides for HLA-A*02:01 and H-2Kb that form stable peptide–MHC I complexes at low temperatures, but dissociate when exposed to a defined elevated temperature. The resulting conditional MHC I complexes, either alone or prepared as ready-to-use multimers, can swiftly be loaded with peptides of choice without additional handling and within a short time frame. We demonstrate the ease and flexibility of this approach by monitoring the antiviral immune constitution in an allogeneic stem cell transplant recipient and by analyzing CD8+ T cell responses to viral epitopes in mice infected with lymphocytic choriomeningitis virus or cytomegalovirus.

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