scholarly journals An N-Acetylated Natural Ligand of Human Histocompatibility Leukocyte Antigen (Hla)-B39

2000 ◽  
Vol 191 (12) ◽  
pp. 2083-2092 ◽  
Author(s):  
Jesús Yagüe ◽  
Iñaki Alvarez ◽  
Didier Rognan ◽  
Manuel Ramos ◽  
Jesús Vázquez ◽  
...  
Keyword(s):  
Mhc Class I ◽  
Essential Feature ◽  
Peptide Binding ◽  
Class I ◽  
High Yield ◽  
Terminal Sequence ◽  
Leukocyte Antigen ◽  
Aminopeptidase M ◽  
Natural Ligand ◽  
Histocompatibility Complex

Sequence-independent interactions involving the free peptidic NH2 terminus are thought to be an essential feature of peptide binding to classical major histocompatibility complex (MHC) class I proteins. Challenging this paradigm, a natural Nα-acetylated ligand of human histocompatibility leukocyte antigen (HLA)-B39 was identified in this study. It matched the NH2-terminal sequence of two human helicases, was resistant to aminopeptidase M, and was produced with high yield from a synthetic 30 mer with the sequence of the putative parental protein by the 20S proteasome. This is the first reported natural ligand of classical MHC class I antigens that has a blocked NH2 terminus.

scholarly journals Porcine major histocompatibility complex (MHC) class I molecules and analysis of their peptide-binding specificities

2011 ◽  
Vol 63 (12) ◽  
pp. 821-834 ◽  
Author(s):  
Lasse Eggers Pedersen ◽  
Mikkel Harndahl ◽  
Michael Rasmussen ◽  
Kasper Lamberth ◽  
William T. Golde ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class I ◽  
Peptide Binding ◽  
Class I ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Mhc Class I Molecules

Conservation of recognition of antibody and T-cell-defined alloantigens between species of equids

2001 ◽  
Vol 13 (8) ◽  
pp. 635
Author(s):  
Jessica M. Baker ◽  
M. Stidworthy ◽  
Tamara Gull ◽  
Jodi Novak ◽  
Jane M. Miller ◽  
...  
Keyword(s):  
T Cell ◽  
Mhc Class I ◽  
Molecular Techniques ◽  
Class I ◽  
Antigenic Determinants ◽  
Immune Recognition ◽  
Large Measure ◽  
Leukocyte Antigen ◽  
Cellular Assays ◽  
Histocompatibility Complex

Serological and cellular assays and molecular techniques were used to define features of the major histocompatibility complex (MHC) of the donkey. With this information in hand, immune recognition of MHC determinants within and between donkeys and horses was compared. An antibody-mediated, complement-dependent, microcytotoxicity assay using a variety of antisera to donkey histocompatibility antigens, including those induced as a result of intraspecies or interspecies pregnancy in horse mares and jenny donkeys, delineated five donkey leukocyte antigen (DoLA) specificities. Antisera raised across species barriers (horse anti-donkey and donkey anti-horse) recognized polymorphic antigenic determinants in the target species. These determinants were often indistinguishable from polymorphic antigens recognized by alloantisera raised within horses or donkeys. The data indicate that a strong correlation exists between the serological antigenic types identified and the specificity of cytotoxic T lymphocytes raised by lymphocyte co-cultures, either within or between species. Moreover, in an analysis of a small number of donkey MHC class I cDNA gene sequences, no features distinguishing horse or donkey MHC class I molecules were identified. These molecular findings explain in large measure why antibody- and T-cell-defined alloantigen recognition is conserved among these closely related equids.

scholarly journals Human Histocompatibility Leukocyte Antigen (HLA)-G Molecules Inhibit NKAT3 Expressing Natural Killer Cells

1997 ◽  
Vol 185 (3) ◽  
pp. 385-392 ◽  
Author(s):  
Christian Münz ◽  
Nicholas Holmes ◽  
Ashley King ◽  
Yung Wai Loke ◽  
Marco Colonna ◽  
...  
Keyword(s):  
Natural Killer ◽  
Mhc Class I ◽  
Class I ◽  
Specific Expression ◽  
Human Major Histocompatibility Complex ◽  
Leukocyte Antigen ◽  
Histocompatibility Complex ◽  
Mother And Child ◽  
Secondary Function ◽  
Mhc Class I Molecules

The crucial immunological function of the classical human major histocompatibility complex (MHC) class I molecules, human histocompatibility leukocyte antigen (HLA)-A, -B, and -C, is the presentation of peptides to T cells. A secondary function is the inhibition of natural killer (NK) cells, mediated by binding of class I molecules to NK receptors. In contrast, the function of the nonclassical human MHC class I molecules, HLA-E, -F, and -G, is still a mystery. The specific expression of HLA-G in placental trophoblast suggests an important role for this molecule in the immunological interaction between mother and child. The fetus, semiallograft by its genotype, escapes maternal allorecognition by downregulation of HLA-A and HLA-B molecules at this interface. It has been suggested that the maternal NK recognition of this downregulation is balanced by the expression of HLA-G, thus preventing damage to the placenta. Here, we describe the partial inhibition of NK lysis of the MHC class I negative cell line LCL721.221 upon HLA-G transfection. We present three NK lines that are inhibited via the interaction of their NKAT3 receptor with HLA-G and with HLA-Bw4 molecules. Inhibition can be blocked by the anti-NKAT3 antibody 5.133. In conclusion, NK inhibition by HLA-G via NKAT3 may contribute to the survival of the fetal semiallograft in the mother during pregnancy.

scholarly journals MHC class I allele diversity in cynomolgus macaques of Vietnamese origin

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7941
Author(s):  
Shuting Huang ◽  
Xia Huang ◽  
Shuang Li ◽  
Mingjun Zhu ◽  
Min Zhuo
Keyword(s):  
Mhc Class I ◽  
Binding Sites ◽  
Macaca Fascicularis ◽  
Peptide Binding ◽  
Cynomolgus Macaque ◽  
Class I ◽  
Histocompatibility Complex ◽  
Cynomolgus Macaques ◽  
Mhc Alleles ◽  
Potential Recombination Event

Cynomolgus macaques (Macaca fascicularis, Mafa) have been used as important experimental animal models for carrying out biomedical researches. The results of biomedical experiments strongly depend on the immunogenetic background of animals, especially on the diversity of major histocompatibility complex (MHC) alleles. However, there is much less information available on the polymorphism of MHC class I genes in cynomolgus macaques, than is currently available for humans. In this study, we have identified 40 Mafa-A and 60 Mafa-B exons 2 and 3 sequences from 30 unrelated cynomolgus macaques of Vietnamese origin. Among these alleles, 28 are novel. As for the remaining 72 known alleles, 15 alleles are shared with other cynomolgus macaque populations and 32 are identical to alleles previously reported in other macaque species. A potential recombination event was observed between Mafa-A1*091:02 and Mafa-A1*057:01. In addition, the Mafa-A1 genes were found to be more diverse than human HLA-A and the functional residues for peptide binding sites (PBS) or TCR binding sites (TBS) in Mafa-A1 have greater variability than that for non-PBS or non-TBS regions. Overall, this study provides important information on the diversity of Mafa-A and Mafa-B alleles from Vietnamese origin, which may help researchers to choose the most appropriate animals for their studies.

scholarly journals A molecular approach to the identification of cytotoxic T-lymphocyte epitopes within equine herpesvirus 1

2006 ◽  
Vol 87 (9) ◽  
pp. 2507-2515 ◽  
Author(s):  
Julia H. Kydd ◽  
N. J. Davis-Poynter ◽  
J. Birch ◽  
D. Hannant ◽  
J. Minke ◽  
...  
Keyword(s):  
Mhc Class I ◽  
Cytotoxic T Lymphocyte ◽  
Class I ◽  
Target Cells ◽  
Equine Herpesvirus ◽  
Equine Herpesvirus 1 ◽  
Leukocyte Antigen ◽  
Histocompatibility Complex ◽  
Herpesvirus 1 ◽  
Functional Peptide

Equine herpesvirus 1 (EHV-1) causes respiratory and neurological disease and abortion in horses. Animals with high frequencies of cytotoxic T lymphocytes (CTL) show reduced severity of respiratory disease and frequency of abortion, probably by CTL-mediated control of cell-associated viraemia. This study aimed to identify CTL epitopes restricted by selected major histocompatibility complex (MHC) class I alleles expressed in the equine leukocyte antigen (ELA) A3 haplotype. Effector CTL were induced from EHV-1-primed ponies and thoroughbreds with characterized MHC class I haplotypes and screened against P815 target cells transfected with selected EHV-1 genes and MHC class I genes. Targets that expressed EHV-1 gene 64 and the MHC B2 gene were lysed by effector CTL in a genetically restricted manner. There was no T-cell recognition of targets expressing either the MHC B2 gene and EHV-1 genes 2, 12, 14, 16, 35, 63 or 69, or the MHC C1 gene and EHV-1 genes 12, 14, 16 or 64. A vaccinia virus vector encoding gene 64 (NYVAC-64) was also investigated. Using lymphocytes from ELA-A3 horses, the recombinant NYVAC-64 virus induced effector CTL that lysed EHV-1-infected target cells; the recombinant virus also supplied a functional peptide that was expressed by target cells and recognized in an MHC-restricted fashion by CTL induced with EHV-1. This construct may therefore be used to determine the antigenicity of EHV-1 gene 64 for other MHC haplotypes. These techniques are broadly applicable to the identification of additional CTL target proteins and their presenting MHC alleles, not only for EHV-1, but for other equine viruses.

scholarly journals Human leukocyte antigen susceptibility map for SARS-CoV-2

2020 ◽  
Author(s):  
Austin Nguyen ◽  
Julianne K. David ◽  
Sean K. Maden ◽  
Mary A. Wood ◽  
Benjamin R. Weeder ◽  
...  
Keyword(s):  
Human Leukocyte Antigen ◽  
Mhc Class I ◽  
Human Leukocyte ◽  
Hla Typing ◽  
Class I ◽  
Susceptibility Map ◽  
Leukocyte Antigen ◽  
Histocompatibility Complex ◽  
Binding Peptides ◽  
Human Coronaviruses

ABSTRACTGenetic variability across the three major histocompatibility complex (MHC) class I genes (human leukocyte antigen [HLA] A, B, and C) may affect susceptibility to and severity of severe acute respiratory syndrome 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). We execute a comprehensive in silico analysis of viral peptide-MHC class I binding affinity across 145 HLA -A, -B, and -C genotypes for all SARS-CoV-2 peptides. We further explore the potential for cross-protective immunity conferred by prior exposure to four common human coronaviruses. The SARS-CoV-2 proteome is successfully sampled and presented by a diversity of HLA alleles. However, we found that HLA-B*46:01 had the fewest predicted binding peptides for SARS-CoV-2, suggesting individuals with this allele may be particularly vulnerable to COVID-19, as they were previously shown to be for SARS (1). Conversely, we found that HLA-B*15:03 showed the greatest capacity to present highly conserved SARS-CoV-2 peptides that are shared among common human coronaviruses, suggesting it could enable cross-protective T-cell based immunity. Finally, we report global distributions of HLA types with potential epidemiological ramifications in the setting of the current pandemic.IMPORTANCEIndividual genetic variation may help to explain different immune responses to a virus across a population. In particular, understanding how variation in HLA may affect the course of COVID-19 could help identify individuals at higher risk from the disease. HLA typing can be fast and inexpensive. Pairing HLA typing with COVID-19 testing where feasible could improve assessment of viral severity in the population. Following the development of a vaccine against SARS-CoV-2, the virus that causes COVID-19, individuals with high-risk HLA types could be prioritized for vaccination.

scholarly journals Cell-cell adhesion mediated by CD8 and human histocompatibility leukocyte antigen G, a nonclassical major histocompatibility complex class 1 molecule on cytotrophoblasts.

1991 ◽  
Vol 174 (3) ◽  
pp. 737-740 ◽  
Author(s):  
S K Sanders ◽  
P A Giblin ◽  
P Kavathas
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class I ◽  
Protein Tyrosine Kinase ◽  
Cell Receptor ◽  
Class I ◽  
Major Histocompatibility ◽  
Leukocyte Antigen ◽  
Histocompatibility Complex ◽  
Class 1 ◽  
Mhc Class I Molecules

The lymphocyte differentiation marker CD8 acts as a coreceptor with the T cell receptor (TCR) during recognition of peptide presented by major histocompatibility complex (MHC) class I molecules. The functions of CD8 in the TCR complex are thought to be signaling through the association of CD8 with the protein tyrosine kinase p56lck and adhesion to MHC class I through the alpha 3 domain. While the ability of the CD8 alpha/alpha homodimer to bind to classical MHC class I molecules has been shown, it is unclear whether CD8 can also bind nonclassical molecules. Of particular interest is human histocompatibility leukocyte antigen (HLA)-G which is expressed on placental cytotrophoblast cells. These cells do not express HLA-A, -B and -C molecules. In this report, we demonstrate that CD8 can bind to HLA-G. It is possible, therefore, that a cell bearing CD8 may interact with HLA-G-expressing cells.

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>

Sign in / Sign up

Export Citation Format

Share Document