In molecular biology, CD4 (cluster of differentiation 4) is a glycoprotein
Glycoprotein
Glycoproteins are proteins that contain oligosaccharide chains (glycans) covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. Secrete…
T-cell receptor
The T cell receptor or TCR is a molecule found on the surface of T lymphocytes (or T cells) that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules.
Monocyte
Monocytes are a type of leukocyte, or white blood cell. They are the largest type of leukocyte and can differentiate into macrophages and myeloid lineage dendritic cells. As a part of the vertebrate innate immune system monocytes also influence the process of adaptive immunity. There are at least three subclasses of monocytes in human blood based on their phenotypic receptors.
CD4 is expressed on helper T cells and binds to class II MHC proteins, whereas CD8 is expressed on cytotoxic T cells and binds to class I MHC proteins (Figure 24-55).
Full
AnswerWhat cells is CD4 found on?
In molecular biology, CD4 (cluster of differentiation 4) is a glycoprotein that serves as a co-receptor for the T-cell receptor (TCR). CD4 is found on the surface of immune cells such as T helper cells, monocytes, macrophages, and dendritic cells.
Where is protein CD4 found?
CD4 protein also known as cluster of differentiation 4 is a glycoprotein located on the surface of different immune cells such as dendritic cells, macrophages, monocytes and T helper cells.
Is CD4 found on macrophages?
IMPORTANCE The CD4 molecule, as the primary receptor for HIV, plays an important role in HIV pathogenesis. There are many cell types that express CD4 other than the primary HIV target, the CD4+ T cell. Other than allowing HIV infection, the role of the CD4 molecule on human monocytes or macrophages is not known.
Do B cells express CD4?
The CD4 was initially identified by flow cytometry and then confirmed by immunohistochemistry. CD4 is a representative marker for helper T-lymphocytes and is present on a subset of thymocytes, peripheral T cells and monocytes or macrophages. Unlike CD2 and CD5, no B cell fractions are known to express CD4.
What cells express CD4 and CD8?
Introduction. T cells are key components of the adaptive immune system. Mature T cells are generally considered to express either the CD4 or CD8 coreceptor, in addition to their TCR, and consequently, the T cell pool is commonly divided into two subsets, based on expression of either CD4 or CD8.
Do dendritic cells have CD4?
Dendritic cells (DCs), which are representative antigen-presenting cells for CD4 T cells act, not only as sentinels for initiating adaptive immune responses, but also as cardinal regulators of innate immunity [8]. DCs originate from bone marrow hematopoietic stem cells [9].
Why do macrophages have CD4?
Our central hypothesis in this proposal is that CD4 has a role in monocyte/ macrophage differentiation and function by modulating the expression of factors that control cellular development and other immune responses.
Are CD4 cells white blood cells?
CD4 cells are a type of white blood cell. They're also called CD4 T lymphocytes or "helper T cells." That's because they help fight infection by triggering your immune system to destroy viruses, bacteria, and other germs that may make you sick.
What is CD4 cells in blood?
CD4 cells are a type of white blood cell. They're also called CD4 T lymphocytes or "helper T cells." That's because they help fight infection by triggering your immune system to destroy viruses, bacteria, and other germs that may make you sick.
How many CD4 cells are in the human body?
CD4 cell count is a laboratory test that measures the number of CD4 T-cells. The normal range is between 500 to 1500 cells/mm^3.
Where are membrane bound antibodies found?
Together with B and T cells, antibodies comprise the most important part of the adaptive immune system. They occur in two forms: one that is attached to a B cell, and the other, a soluble form, that is unattached and found in extracellular fluids such as blood plasma.
What is CD4 a marker for?
Also known as T4, and Leu-3, CD4 is a 55 kDa type I transmembrane glycoprotein and member of the immunoglobulin superfamily. Primarily described as a marker for T cell subsets it can also be found on NKT cells, innate lymphoid cells and macrophages.
Which type of lymphocytes express selective cytoplasmic expression?
Selective cytoplasmic expression in peripheral lymphocytes and subsets of cells in lymphoid tissues.
What is the role of membrane glycoprotein in the immune system?
Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in resp onses against both external and internal offenses. In T-cells, functions primarily as a coreceptor for MHC class II molecule:peptide complex.
What is the protein browser?
The protein browser displays the antigen location on the target protein (s) and the features of the target protein. The tabs at the top of the protein view section can be used to switch between the different splice variants to which an antigen has been mapped.
What does the yellow triangle on the protein bar mean?
A yellow triangle on the bar indicates a <100% sequence identity to the protein target.
What is CD4 in biology?
Image of CD4 co-receptor binding to MHC (Major Histocompatibility Complex) non-polymorphic region. In molecular biology, CD4 ( cluster of differentiation 4) is a glycoprotein that serves as a co-receptor for the T-cell receptor (TCR). CD4 is found on the surface of immune cells such as T helper cells, ...
What is the CD4 gene?
In humans, the CD4 protein is encoded by the CD4 gene. CD4+ T helper cells are white blood cells that are an essential part of the human immune system. They are often referred to as CD4 cells, T-helper cells or T4 cells.
What are the co-receptors of HIV?
These co-receptors are chemokine receptors CCR5 or CXCR4. Following a structural change in another viral protein ( gp41 ), HIV inserts a fusion peptide into the host cell that allows the outer membrane of the virus to fuse with the cell membrane .
What is the CD4 receptor?
Schematic representation of CD4 receptor. Like many cell surface receptors/markers, CD4 is a member of the immunoglobulin superfamily . It has four immunoglobulin domains (D 1 to D 4) that are exposed on the extracellular surface of the cell: D 1 and D 3 resemble immunoglobulin variable (IgV) domains. D 2 and D 4 resemble immunoglobulin constant ...
How many cells are in a normal blood count for HIV?
National Institutes of Health guidelines recommend treatment of any HIV-positive individuals, regardless of CD4 count Normal blood values are usually expressed as the number of cells per microliter (μL, or equivalently, cubic millimeter, mm 3) of blood, with normal values for CD4 cells being 500–1200 cell s/mm 3.
How does HIV-1 use CD4?
HIV-1 uses CD4 to gain entry into host T-cells and achieves this through its viral envelope protein known as gp120. The binding to CD4 creates a shift in the conformation of gp120 allowing HIV-1 to bind to a co-receptor expressed on the host cell. These co-receptors are chemokine receptors CCR5 or CXCR4. Following a structural change in another viral protein ( gp41 ), HIV inserts a fusion peptide into the host cell that allows the outer membrane of the virus to fuse with the cell membrane .
Where is CD4 found?
CD4 is found on the surface of immune cells such as T helper cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 ...
What is CD4 T cell?
Latesha Elopre, MD, MSPH. on July 23, 2020. T-cells are a subset of white blood cells that play an important role in the body's immune system. CD4 is, by contrast, a type of protein found on certain immune cells like T-cells, macrophages, and monocytes. CD4 T-cells are considered "helper" cells ...
Why are CD4 T cells considered helpers?
CD4 T-cells are considered "helper" cells because they do not neutralize infections but rather trigger the body's response to infections. 1 In response, CD8 T-cells—classified as such because of the type of protein on their surface—play the part of "killer" cells by producing substances (antibodies) that help fight off viruses and other foreign invaders.
What is the role of CD4 T cells in HIV?
One of the conundrums of HIV infection is that the very cells meant to initiate an immune defense are the same ones targeted for infection by HIV. As a retrovirus, HIV needs to infect certain "host" cells in order to make copies of itself. CD4 cells are the prime targets for this in the course of an infection.
How many CD4 cells are needed for AIDS?
2 . In a healthy adult, a normal CD4 count can vary enormously (by population, age group, etc.) but is typically around 500 to 1500 cells per cubic millimeter of blood (mL). When it falls below 200, however, then the disease is technically classified as AIDS ...
How to determine if a person has a CD4?
By measuring how many functioning CD4 cells are circulating in the blood, a doctor can determine the status of a person's immune system. A simple blood test called the CD4 count estimates the number of functioning CD4 cells in a cubic millimeter of blood. The higher the CD4 count, the stronger the immune function. 2
Is CD4 T cell one cell?
More often than not we tend to think of CD4 T-cells as one type of cell. In fact, it was only in the mid-1980s that scientists began identifying various subsets with different functions.
What are the three types of proteins that are present on the surface of a T cell?
Antigen-presenting cells display three types of proteinmolecules on their surface that have a role in activating a T cell to become an effector cell: (1) MHCproteins, which present foreign antigento the T cell receptor, (2) costimulatory proteins ,which bind to complementaryreceptors on the T cell surface, and (3) cell-cell adhesion molecules,which enable a T cell to bind to the antigen-presenting cellfor long enough to become activated (Figure 24-44).
Which proteases enter the cytosol through the perforin channels?
The secretory vesicles also contain serine proteases, which are thought to enter the target cell cytosolthrough the perforin channels. One of the proteases, called granzyme B,cleaves, and thereby activates, one or more members of the caspasefamilyof proteases that mediate apoptosis.
How do cytotoxic T cells kill?
The binding alters the Fas proteins so that their clustered cytosolic tails recruit procaspase-8 into the complexvia an adaptor protein. The recruited procaspase-8 molecules cross-cleave and activate each other to begin the caspase cascade that leads to apoptosis(Figure 24-46B). Cytotoxic T cells apparently use this killing strategy to help contain an immune responseonce it is well underway, by killing excessive effector lymphocytes, especially effector T cells: if the geneencoding either Fas or Fas ligand is inactivated by mutation, effector lymphocytes accumulate in vast numbers in the spleen and lymphnodes, which become enormously enlarged.
What does the effector T cell do?
Effector cytotoxic T cellsdirectly kill cells that are infected with a virusor some other intracellular pathogen. Effector helper T cells,by contrast, help stimulate the responses of other cells—mainly macrophages, B cells, and cytotoxic T cells.
How do T cells kill?
Once bound to its target cell, a cytotoxic T cellcan employ at least two strategies to kill the target, both of which operate by inducing the target cell to kill itself by undergoing apoptosis(discussed in Chapter 17). In killing an infected target cell, the cytotoxic T cell usually releases a pore-forming proteincalled perforin, which is homologousto the complement component C9 (see Figure 25-42) and polymerizes in the target cell plasma membraneto form transmembrane channels. Perforin is stored in secretory vesicles of the cytotoxic T cell and is released by local exocytosisat the point of contact with the target cell. The secretory vesicles also contain serine proteases, which are thought to enter the target cell cytosolthrough the perforin channels. One of the proteases, called granzyme B,cleaves, and thereby activates, one or more members of the caspasefamilyof proteases that mediate apoptosis. These caspases then activate other caspases, producing a proteolytic cascade that helps kill the cell (discussed in Chapter 17) (Figure 24-46A). Mice in which the perforin geneis inactivated cannot generate microbe-specific cytotoxic T cells and show increased susceptibility to certain viral and intracellular bacterial infections.
Why are T cells difficult to isolate?
Because T cell responses depend on direct contact with an antigen-presenting cellor a target cell, the antigen receptors made by T cells , unlike antibodies made by B cells, exist only in membrane-bound form and are not secreted. For this reason, T cell receptors were difficult to isolate, and it was not until the 1980s that they were first identified biochemically. On both cytotoxic and helper T cells, the receptors are similar to antibodies. They are composed of two disulfide-linked polypeptidechains (called α and β), each of which contains two Ig-like domains, one variable and one constant (Figure 24-42A). Moreover, the three-dimensional structure of the extracellular part of a T cell receptorhas been determinedby x-ray diffraction, and it looks very much like one arm of a Y-shaped antibody molecule(Figure 24-42B).
Why do T cells respond to antigens?
The T cells respond in this manner because the form of antigen they recognize is different from that recognized by B cells. Whereas B cells recognize intact antigen, T cells recognize fragments of proteinantigens that have been partly degraded inside the antigen-presenting cell. The peptide fragments are then carried to the surface ...
Overview
In molecular biology, CD4 (cluster of differentiation 4) is a glycoprotein that serves as a co-receptor for the T-cell receptor (TCR). CD4 is found on the surface of immune cells such as T helper cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 (after the OKT4 monoclonal antibody that reacted with it) before being named …
Structure
Like many cell surface receptors/markers, CD4 is a member of the immunoglobulin superfamily.
It has four immunoglobulin domains (D1 to D4) that are exposed on the extracellular surface of the cell:
• D1 and D3 resemble immunoglobulin variable (IgV) domains.
Function
CD4 is a co-receptor of the T cell receptor (TCR) and assists the latter in communicating with antigen-presenting cells. The TCR complex and CD4 bind to distinct regions of the antigen-presenting MHC class II molecule. The extracellular D1 domain of CD4 binds to the β2 region of MHC class II. The resulting close proximity between the TCR complex and CD4 allows the tyrosine kinase Lck bound to the cytoplasmic tail of CD4 to phosphorylate tyrosine residues of immunore…
Disease
HIV-1 uses CD4 to gain entry into host T-cells and achieves this through its viral envelope protein known as gp120. The binding to CD4 creates a shift in the conformation of gp120 allowing HIV-1 to bind to a co-receptor expressed on the host cell. These co-receptors are chemokine receptors CCR5 or CXCR4. Following a structural change in another viral protein (gp41), HIV inserts a fusion peptide i…
See also
• CD4+ T cells and antitumor immunity
Further reading
• Miceli MC, Parnes JR (1993). "Role of CD4 and CD8 in T cell activation and differentiation". Advances in Immunology Volume 53. Advances in Immunology. Vol. 53. pp. 59–122. doi:10.1016/S0065-2776(08)60498-8. ISBN 978-0-12-022453-1. PMID 8512039.
• Geyer M, Fackler OT, Peterlin BM (July 2001). "Structure--function relationships in HIV-1 Nef". EMBO Reports. 2 (7): 580–5. doi:10.1093/embo-reports/kve141. PMC 1083955. PMID 11463741.
External links
• CD1+Antigen at the US National Library of Medicine Medical Subject Headings (MeSH)
• Mouse CD Antigen Chart
• Human CD Antigen Chart
• Human Immunodeficiency Virus Glycoprotein 120
Mechanism of action
T-cells are a subset of white blood cells that play an important role in the body's immune system. CD4 is, by contrast, a type of protein found on the certain immune cells like T-cells, macrophages, and monocytes.
Function
- CD4 T-cells are considered \"helper\" cells because they do not neutralize infections but rather triggers the body's response to infections. In response, CD8 T-cellsclassified as such because of the type of protein on their surfaceplay the part of \"killer\" cells by producing substances (antibodies) that help fight off viruses and other foreign invaders.
Pathophysiology
- One of the conundrums of HIV infection is that the very cells meant to initiate an immune defense are the same ones targeted for infection by HIV. As a retrovirus, HIV needs to infect certain \"host\" cells in order to make copies of itself. CD4 cells are the prime targets for this in the course of an infection. During infection, HIV attaches to these helper cells, emptying its genetic …
Types
- More often than not we tend to think of CD4 T-cells as one type of cell. In fact, it was only in the mid-1980s that scientist began identifying various subsets with different functions. Some are important in activating so-called macrophage and dendritic cells during initial infection, while others direct immune defenses when faced, individually, with parasitic organisms, bacteria, or vi…
Diagnosis
- By determining how many functioning CD4 cells are circulating in the blood, a doctor can determine the status of a person's immune system. A simple blood test called the CD4 count estimates the number of functioning CD4 cells in a cubic millimeter of blood. The higher the CD4 count, the stronger the immune function.
Epidemiology
- In a healthy adult, a normal CD4 count can vary enormously (by population, age group, etc.) but is typically around 500 to 1500 cells per cubic millimeter of blood (mL). When it falls below 200, however, then the disease is technically classified as AIDS (acquired immune deficiency syndrome). It is during this time that the most serious opportunistic infections are known to occ…
Medical uses
- Prior to 2016, CD4 counts had been used as a means by which to determine when to start antiretroviral therapy. But in recent years that role has been changed as global authorities now endorse the immediate initiation of HIV therapy on diagnosis (rather than waiting until the CD4 count dropped below 500 cells/mL, as was the previous guideline).
Clinical significance
- The CD4 count is also used to monitor an individual's response to therapy, with earlier initiation of antiretroviral therapy generally able to restore a person's immune function. By contrast, people starting therapy at very low CD4 counts (under 100 cells/mL) often have a more difficult time reconstituting their CD4 counts to normal levels, particularly after a severe bout of illness.
Significance
- It is, therefore, important to get tested and seek immediate care in the event of an HIV-positive diagnosis. If treatment is started promptly, people living with HIV now have a far better chance of living normal and healthy life spans.
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