A5038466528- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- vaccines and immunoinformatics approaches
- Cytomegalovirus and herpesvirus research
- Monoclonal and Polyclonal Antibodies Research
- HIV Research and Treatment
- Hepatitis B Virus Studies
- Immune Response and Inflammation
- Animal Virus Infections Studies
- Peptidase Inhibition and Analysis
- interferon and immune responses
- Hepatitis Viruses Studies and Epidemiology
- Pharmacological Effects of Natural Compounds
- Endoplasmic Reticulum Stress and Disease
- Herpesvirus Infections and Treatments
- Respiratory viral infections research
- Reproductive System and Pregnancy
- Drug-Induced Adverse Reactions
- Escherichia coli research studies
- Viral-associated cancers and disorders
- T-cell and Retrovirus Studies
- COVID-19 Impact on Reproduction
- Soybean genetics and cultivation
- Galectins and Cancer Biology
University of Southampton
2010-2023
The Pirbright Institute
2005-2015
Southampton General Hospital
2010
University of Southern Denmark
2005
Organic Research Centre
2005
Our understanding of the antigen presentation pathway has recently been enhanced with identification that tapasin-related protein TAPBPR is a second major histocompatibility complex (MHC) class I-specific chaperone. We sought to determine whether, like tapasin, can also influence MHC I peptide selection by functioning as exchange catalyst. show catalyse dissociation peptides from peptide-MHC complexes, enhance loading peptide-receptive molecules, and discriminate between based on affinity in...
Recently, we revealed that TAPBPR is a peptide exchange catalyst important for optimal selection by MHC class I molecules. Here, asked whether any other co-factors associate with TAPBPR, which would explain its effect on selection. We identify an interaction between and UDP-glucose:glycoprotein glucosyltransferase 1 (UGT1), folding sensor in the calnexin/calreticulin quality control cycle known to regenerate Glc
The intracellular trafficking of major histocompatibility complex class I (MHC-I) proteins is directed by three quality control mechanisms that test for their structural integrity, which correlated to the binding high-affinity antigenic peptide ligands. To investigate molecular features MHC-I these detect, we have followed hypothesis suboptimally loaded are characterized conformational mobility in F pocket region site. We created a novel variant an protein, Kb-Y84C, two alpha helices this...
CD1 molecules play an important role in the immune system, presenting lipid-containing antigens to T and NKT cells. genes have long been thought be as ancient MHC class I II genes, based on various arguments, but thus far they described only mammals. Here we describe two chickens, demonstrating that system was present last common ancestor of mammals birds at least 300 million years ago. In phylogenetic analysis, these sequences cluster with from other species are not obviously like any...
Abstract Compared with the MHC of typical mammals, chicken (BF/BL region) B12 haplotype is smaller, simpler, and rearranged, two classical class I genes which only one highly expressed. In this study, we describe development long-distance PCR to amplify some or all each gene separately, allowing us make following points. First, six other haplotypes have same genomic organization as B12, a poorly expressed (minor) BF1 between DMB2 TAP2 well-expressed (major) BF2 C4. Second, expression...
<ns4:p>We have known since the late 1980s that function of classical major histocompatibility complex (MHC) class I molecules is to bind peptides and display them at cell surface cytotoxic T cells. Recognition by these sentinels immune system can lead destruction presenting cell, thus protecting host from pathogens cancer. Classical MHC (MHC hereafter) are co-dominantly expressed, polygenic, exceptionally polymorphic significant sequence diversity. Thus, in most species, there many different...
The biggest roadblock in development of effective vaccines against human immunodeficiency virus type 1 (HIV-1) is the genetic diversity. For T-cell vaccine, this can be tackled by focusing vaccine-elicited T-cells on highly functionally conserved regions HIV-1 proteins, mutations which typically cause a replicative fitness loss, and computing multivalent mosaic maximize coverage potential 9-mer epitopes input viral sequences. Our first region HIVconsv employed clade alternating consensus...
Significance Major histocompatibility complex (MHC) molecules play crucial roles in the immune response to pathogens and tumors by presenting protein fragments (peptides) T lymphocytes. Recently, it has become clear that breadth of peptide presentation MHC class I is inversely correlated with level cell surface expression, a relationship resistance Marek’s disease chickens progression AIDS humans. In this article, evidence presented vary suite properties, including thermostability, are...
In contrast to typical mammals, the chicken MHC (the BF-BL region of B locus) has strong genetic associations with resistance and susceptibility infectious pathogens as well responses vaccines. We have shown that encodes a single dominantly expressed class I molecule whose peptide-binding motifs can determine viral pathogens, such Rous sarcoma virus Marek's disease virus. this report, we examine response molecular defined vaccine, fp-IBD1, which consists fowlpox vector carrying VP2 gene...
Major histocompatibility complex class I molecules (MHC I) present peptides to cytotoxic T-cells at the surface of almost all nucleated cells. The function MHC is select high affinity from a large intracellular pool and they are assisted in this process by co-factor molecules, notably tapasin. In contrast mammals, homozygous chickens express single gene locus, termed BF2, which hypothesised have co-evolved with highly polymorphic tapasin within stable haplotypes. BF2 B15 B19 haplotypes...
Abacavir hypersensitivity syndrome can occur in individuals expressing the HLA-B*57:01 major histocompatibility complex class I allotype when utilising drug abacavir as a part of their anti-retroviral regimen. The is known to bind within antigen binding cleft, leading selection novel self-peptide ligands, thus provoking life-threatening immune responses. However, sub-cellular location and mechanics altered peptide are not well understood. Here, we probed impact on assembly complexes. We show...
ADVERTISEMENT RETURN TO ISSUEViewpointNEXTProtein Plasticity and Peptide Editing in the MHC I Antigen Processing PathwayTim Elliott*Tim ElliottInstitute for Life Sciences Centre Cancer Immunology, Faculty of Medicine, University Southampton, Southampton SO16 6YD, U.K.*University Hospital Tremona Road, United Kingdom. Telephone: 44-23-8120-6184. Fax: 44-23-8120-5152. E-mail: [email protected]More by Tim Elliotthttp://orcid.org/0000-0003-1097-0222 Andy van HaterenAndy HaterenInstitute U.K.More...
Drug development typically comprises a combination of pre-clinical experimentation, clinical trials, and statistical data-driven analyses. Therapeutic failure in late-stage costs the pharmaceutical industry billions USD per year. Clinical trial simulation represents key derisking strategy combining them with mechanistic models allows one to test hypotheses for mechanisms improve designs. This is illustrated T-cell activation model, used simulate trials IMA901, short-peptide cancer vaccine....