Hidde Ploegh | |
|---|---|
 Hidde Ploegh (2017) | |
| Alma mater | University of Groningen, University of Leiden |
| Scientific career | |
| Fields | Immunology |
| Institutions | Boston Children's Hospital |
| Doctoral advisor | Jack Strominger |
Hidde Lolke Ploegh (born 7 January 1953) is an immunologist at Boston Children's Hospital, known for his contributions in understanding antigen processing and the evasion of the immune system by viruses.
Ploegh, a native of the Netherlands, received a Bachelor of Science degree in 1975, and a Master of Science degree in biology and chemistry in 1977, from the University of Groningen. Having worked for six months in Jack Strominger's lab at that time, he was able to continue his PhD studies under Strominger and received a doctorate from the University of Leiden. Ploegh would then go on to hold positions at a number of institutions such as the University of Cologne, the Netherlands Cancer Institute, Utrecht University (2012–2015), [1] and Harvard Medical School, before becoming a member of the Whitehead Institute. [2] [3]
In 1986 Ploegh became a member of the European Molecular Biology Organization. [4] In 1997 Ploegh became a corresponding member of the Royal Netherlands Academy of Arts and Sciences. [5] In 2016 he was elected to the National Academy of Sciences. [6]
Much of the research by Ploegh is in the fields of biochemistry and immunology. Earlier in his career, Ploegh's research focused on the ability of MHC molecules, such as MHC-II, to interact with antigen peptides inside a cell. [7]
More recently, the Ploegh lab at the Whitehead Institute has been using a technique called “sortagging” to look at the pathways through which viruses are able to avoid detection by the immune system. Memory B cells are lymphocytes known to be produced to fight off secondary infection, yet the influenza virus is able to avoid the immune response generated by these cells. This method was used to tag the influenza virus, so that it could be observed, and it was found that the interaction of virus antigens with the B-cell receptor is required for infection. [8] [9]
Ploegh has also been involved in developing therapeutic roles for sortagging. Erythrocytes are the most abundant cell type found in the body known for lacking nuclei as a mature cell. This makes them ideal for the delivery of drugs through the body as they cannot mutate as a mature cell. Ploegh and his colleagues have been able to use sortase to cut erythrocyte surface proteins, allowing the binding of biotin and its circulation throughout the body. As sortagging allows the binding of a number of different proteins, it may be used for the binding of antibodies and their delivery to target sites in the body. [10] [11]
In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response.
A DNA vaccine is a type of vaccine that transfects a specific antigen-coding DNA sequence into the cells of an organism as a mechanism to induce an immune response.
A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular pathogens (such as viruses or bacteria), or cells that are damaged in other ways.
The major histocompatibility complex (MHC) is a large locus on vertebrate DNA containing a set of closely linked polymorphic genes that code for cell surface proteins essential for the adaptive immune system. These cell surface proteins are called MHC molecules.
Antigenic drift is a kind of genetic variation in viruses, arising from the accumulation of mutations in the virus genes that code for virus-surface proteins that host antibodies recognize. This results in a new strain of virus particles that is not effectively inhibited by the antibodies that prevented infection by previous strains. This makes it easier for the changed virus to spread throughout a partially immune population. Antigenic drift occurs in both influenza A and influenza B viruses.
Don Craig Wiley was an American structural biologist.
The adaptive immune system, also known as the acquired immune system, or specific immune system is a subsystem of the immune system that is composed of specialized, systemic cells and processes that eliminate pathogens or prevent their growth. The acquired immune system is one of the two main immunity strategies found in vertebrates.
MHC class I molecules are one of two primary classes of major histocompatibility complex (MHC) molecules and are found on the cell surface of all nucleated cells in the bodies of vertebrates. They also occur on platelets, but not on red blood cells. Their function is to display peptide fragments of proteins from within the cell to cytotoxic T cells; this will trigger an immediate response from the immune system against a particular non-self antigen displayed with the help of an MHC class I protein. Because MHC class I molecules present peptides derived from cytosolic proteins, the pathway of MHC class I presentation is often called cytosolic or endogenous pathway.
β2 microglobulin (B2M) is a component of MHC class I molecules. MHC class I molecules have α1, α2, and α3 proteins which are present on all nucleated cells. In humans, the β2 microglobulin protein is encoded by the B2M gene.
Pamela Jane Bjorkman NAS, AAAS is an American biochemist. She is the David Baltimore Professor of Biology and Biological Engineering at the California Institute of Technology (Caltech), Her research centers on the study of the three-dimensional structures of proteins related to Class I MHC, or Major Histocompatibility Complex, proteins of the immune system and proteins involved in the immune responses to viruses. Bjorkman is most well known as a pioneer in the field of structural biology.
Antigen presentation is a vital immune process that is essential for T cell immune response triggering. Because T cells recognize only fragmented antigens displayed on cell surfaces, antigen processing must occur before the antigen fragment can be recognized by a T-cell receptor. Specifically, the fragment, bound to the major histocompatibility complex (MHC), is transported to the surface of the cell, a process known as presentation. If there has been an infection with viruses or bacteria, the cell will present an endogenous or exogenous peptide fragment derived from the antigen by MHC molecules. There are two types of MHC molecules which differ in the behaviour of the antigens: MHC class I molecules (MHC-I) bind peptides from the cell cytosol, while peptides generated in the endocytic vesicles after internalisation are bound to MHC class II (MHC-II). Cellular membranes separate these two cellular environments - intracellular and extracellular. Each T cell can only recognize tens to hundreds of copies of a unique sequence of a single peptide among thousands of other peptides presented on the same cell, because an MHC molecule in one cell can bind to quite a large range of peptides. Predicting which antigens will be presented to the immune system by a certain MHC/HLA type is difficult, but the technology involved is improving.
HLA-A is a group of human leukocyte antigens (HLA) that are encoded by the HLA-A locus, which is located at human chromosome 6p21.3. HLA is a major histocompatibility complex (MHC) antigen specific to humans. HLA-A is one of three major types of human MHC class I transmembrane proteins. The others are HLA-B and HLA-C. The protein is a heterodimer, and is composed of a heavy α chain and smaller β chain. The α chain is encoded by a variant HLA-A gene, and the β chain (β2-microglobulin) is an invariant β2 microglobulin molecule. The β2 microglobulin protein is encoded by the B2M gene, which is located at chromosome 15q21.1 in humans.
A tetramer assay is a procedure that uses tetrameric proteins to detect and quantify T cells that are specific for a given antigen within a blood sample. The tetramers used in the assay are made up of four major histocompatibility complex (MHC) molecules, which are found on the surface of most cells in the body. MHC molecules present peptides to T-cells as a way to communicate the presence of viruses, bacteria, cancerous mutations, or other antigens in a cell. If a T-cell's receptor matches the peptide being presented by an MHC molecule, an immune response is triggered. Thus, MHC tetramers that are bioengineered to present a specific peptide can be used to find T-cells with receptors that match that peptide. The tetramers are labeled with a fluorophore, allowing tetramer-bound T-cells to be analyzed with flow cytometry. Quantification and sorting of T-cells by flow cytometry enables researchers to investigate immune response to viral infection and vaccine administration as well as functionality of antigen-specific T-cells. Generally, if a person's immune system has encountered a pathogen, the individual will possess T cells with specificity toward some peptide on that pathogen. Hence, if a tetramer stain specific for a pathogenic peptide results in a positive signal, this may indicate that the person's immune system has encountered and built a response to that pathogen.
Antonio Lanzavecchia is an Italian and Swiss immunologist. As a fellow of Collegio Borromeo he obtained a degree with honors in Medicine in 1976 from the University of Pavia where he specialized in Pediatrics and Infectious Diseases. He is Head Human Immunology Program, Istituto Nazionale di Genetica Molecolare-INGM, Milan and SVP Senior research Fellow, Humabs/Vir Biotechnology, Bellinzona and San Francisco (USA). Since 2017, he is also Professor at the Faculty of Biomedical Sciences of the Università della Svizzera italiana (USI).
HLA-DM is an intracellular protein involved in the mechanism of antigen presentation on antigen presenting cells (APCs) of the immune system. It does this by assisting in peptide loading of major histocompatibility complex (MHC) class II membrane-bound proteins. HLA-DM is encoded by the genes HLA-DMA and HLA-DMB.
HLA class II histocompatibility antigen gamma chain also known as HLA-DR antigens-associated invariant chain or CD74, is a protein that in humans is encoded by the CD74 gene. The invariant chain is a polypeptide which plays a critical role in antigen presentation. It is involved in the formation and transport of MHC class II peptide complexes for the generation of CD4+ T cell responses. The cell surface form of the invariant chain is known as CD74. CD74 is a cell surface receptor for the cytokine macrophage migration inhibitory factor (MIF).
Jack Leonard Strominger is the Higgins Professor of Biochemistry at Harvard University, specializing in the structure and function of human histocompatibility proteins and their role in disease. He won the Albert Lasker Award for Basic Medical Research in 1995.
Immunoevasins are proteins expressed by some viruses that enable the virus to evade immune recognition by interfering with MHC I complexes in the infected cell, therefore blocking the recognition of viral protein fragments by CD8+ cytotoxic T lymphocytes. Less frequently, MHC II antigen presentation and induced-self molecules may also be targeted. Some viral immunoevasins block peptide entry into the endoplasmic reticulum (ER) by targeting the TAP transporters. Immunoevasins are particularly abundant in viruses that are capable of establishing long-term infections of the host, such as herpesviruses.
MHC multimers are oligomeric forms of MHC molecules, designed to identify and isolate T-cells with high affinity to specific antigens amid a large group of unrelated T-cells. Multimers generally range in size from dimers to octamers; however, some companies use even higher quantities of MHC per multimer. Multimers may be used to display class 1 MHC, class 2 MHC, or nonclassical molecules from species such as monkeys, mice, and humans.
Carol Shoshkes Reiss, an American viral immunologist, has been professor in New York University's department of biology since 1991. Her research focused on the dynamic contest between the mouse immune system and virus replication during infection of the central nervous system. Reiss was editor-in-chief of the journal Viral Immunology (2000–2006) and is currently editor-in-chief of the journal DNA and Cell Biology (2012–present).
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