120 Questions
What is the structure of MHC class I antigens?
A pair of non-identical heavy chains (α and β)
How many amino acids long are the peptides that can be tightly bound to a groove in MHC class I antigens?
Nine
What is the function of the groove produced by the pairing of the two extracellular domains of the α chain?
To bind to peptides
What determines the affinity of individual peptide binding to MHC class I antigens?
The nature and shape of the groove
Which of the following is NOT a characteristic of MHC class I antigens?
They have two heavy chains
What is the name of the molecule that pairs with the α chain to form the groove in MHC class I antigens?
β2m
What technique was used to determine the detailed structure of MHC class II antigens?
X-ray crystallography
Which chromosome contains the genes that code for MHC class I and class II antigens?
Chromosome 6
What is the function of TAP in the context of MHC Class I molecules?
To transport peptides into the endoplasmic reticulum
How do MHC Class I molecules interact with viral peptide antigens?
Through the binding of viral peptide to the groove of the MHC Class I molecule
What is the function of the invariant chain in MHC Class II molecules?
To protect the MHC Class II molecule from binding to antigen
What is the approximate number of amino acids in each domain of the immunoglobulin molecule?
110
What is the purpose of the disulphide bond between two cysteine residues in the immunoglobulin chain?
To hold the domains together in a loop
Where do MHC Class I molecules bind to viral peptide antigens?
In the endoplasmic reticulum
What determines the isotype of the immunoglobulin?
The heavy chain
What is the role of the vesicle in the context of MHC Class II molecules?
To fuse with the endosome to allow antigen processing
Where is the carbohydrate side chain found in MHC class I antigens?
Between the α and β chains
What is the term used to describe the recognition of peptide and MHC molecule by T cells?
MHC restriction
What is the function of β2-microglobulin in MHC class I antigens?
To form a complex with the α chain
What is the importance of MHC restriction in the immune response?
It restricts the ability of T cells to recognize antigens
What is the name of the Nobel Prize winners who discovered MHC restriction?
Peter Doherty and Rolf Zinkernagel
How many groups are MHC class I antigens subdivided into?
Three
What are the three groups of variable class II antigens in humans?
HLA-DP, HLA-DQ, HLA-DR
What induces the expression of class II molecules on certain cells?
Interferon-γ
What is the location of the carbohydrate side chain in MHC class I antigens?
Between the α and β chains
What is the name of the molecule that pairs with the α chain in MHC class I antigens?
β2-microglobulin
Which of the following cell types expresses MHC class I molecules?
Most nucleated cells
What is the term used to describe the recognition of peptide and MHC molecule by T cells?
MHC restriction
How many groups are MHC class I antigens subdivided into?
3
What is the importance of MHC restriction in the immune response?
It restricts the ability of T cells to recognize antigen
What is the name of the Nobel Prize winners who discovered MHC restriction?
Peter Doherty and Rolf Zinkernagel
What induces the expression of class II molecules on certain cells?
Interferon-γ
What is the structural feature of MHC class I antigens that allows it to bind to peptides?
A groove formed by the pairing of the two extracellular domains of the α chain
What is the component that pairs with the α chain to form the groove in MHC class I antigens?
β2-microglobulin
How many amino acids long are the peptides that can be tightly bound to a groove in MHC class I antigens?
8-11 amino acids
What determines the affinity of individual peptide binding to MHC class I antigens?
The nature and shape of the groove
What is the name of the molecule that helps to form the groove in MHC class I antigens?
β2-microglobulin
What is the function of the groove in MHC class I antigens?
To bind to the peptide antigen
What is the characteristic of the peptides that can be tightly bound to a groove in MHC class I antigens?
They are 8-11 amino acids long
What is the function of MHC class I antigens?
To present peptide antigens to T cells
What is the purpose of the TAP in the context of MHC Class I molecules?
To transport viral peptides from the endoplasmic reticulum to the cytosol
Where are MHC Class I molecules loaded with viral peptides?
In the endoplasmic reticulum
What is the function of the MHC class I molecule?
To present viral peptides to CD8+ T cells
What is the result of the interaction between MHC Class I molecules and viral peptides?
Activation of CD8+ T cells
Where are the genes that code for MHC class I molecules located?
On chromosome 6
What is the role of the endoplasmic reticulum in the context of MHC class I molecules?
To load MHC class I molecules with viral peptides
What is the function of β2-microglobulin in the context of MHC class I molecules?
To stabilize the MHC class I molecule
What is the result of the binding of viral peptides to MHC class I molecules?
Presentation of viral peptides to CD8+ T cells
How many chains do MHC class II antigens have?
Two heavy chains (α and β)
Where are the genes that code for MHC class II antigens located?
Chromosome 6
How was the detailed structure of MHC class II antigens determined?
X-ray crystallography
What is the characteristic of the structure of MHC class II antigens?
A folded structure
What is the name of the molecule that pairs with the α chain to form the groove in MHC class I antigens?
β2-microglobulin
How many amino acids long can peptides be that are tightly bound to a groove in MHC class I antigens?
Nine amino acids
What determines the affinity of individual peptide binding to MHC class I antigens?
The shape of the groove
What is the name of the region of chromosome 6 where MHC class I and II genes are located?
MHC region
Which cells are restricted to express MHC class II molecules?
Dendritic cells, B lymphocytes, activated T cells, macrophages, and some epithelial cells
What is the name of the loci that are known for the three groups of variable class II antigens in humans?
HLA-DP, HLA-DQ, HLA-DR
Under what condition can other cells be induced to express class II molecules?
During inflammation
What is the function of MHC class II molecules in the immune response?
To present antigens to CD4+ T cells
What is the characteristic of cells that express MHC class II molecules?
They are able to present antigens to CD4+ T cells
What is the result of the interaction between MHC class II molecules and antigens?
Activation of CD4+ T cells
What is the role of MHC class II molecules in the immune response?
To present antigens to CD4+ T cells
What is the role of the invariant chain in the context of MHC Class II molecules?
To protect the MHC class II molecule from binding to antigen in the groove
What is the significance of MHC class II molecules in the immune response?
They are involved in the presentation of antigens to CD4+ T cells
Where are MHC Class II molecules loaded with antigen?
Endosome
What is the structure of the domains in MHC Class II molecules?
A loop held together by a disulphide bond between two cysteine residues
What is the function of the vesicle in the context of MHC Class II molecules?
To fuse with the endosome to deliver antigen to MHC class II molecules
How do MHC Class II molecules interact with antigen?
By binding to the antigen in the groove
What is the characteristic of the antigen that can be bound to MHC Class II molecules?
It is a processed exogenous antigen
Where are the genes that code for MHC Class II molecules located?
On an autosome
What is the function of MHC Class II molecules?
To present exogenous antigen to T cells
What type of T cells recognize antigens presented by MHC class II molecules?
CD4+
What is the function of β2-microglobulin in MHC class I antigens?
To associate with the α chain
What prevents MHC class II molecules from binding to peptides in the endoplasmic reticulum?
Invariant chain
What is the function of MHC class I molecules?
To present endogenous antigens to CD8+ T cells
What determines the differences between individual MHC class I antigens?
Variations in the α chain
What is the structure of the immunoglobulin molecule?
Two heavy chains and two light chains
What is the role of antigen-presenting cells (APCs) in the context of MHC class I antigens?
To present antigens to T cells
What is the purpose of the peptide binding groove in MHC class I antigens?
To present antigens to T cells
Where are the genes that code for MHC class II antigens located?
Chromosome 6
What type of antigens are processed by the lysosomal route and presented by MHC class II antigens?
Exogenous antigens
What type of bonding is used to determine the detailed structure of MHC class I antigens?
X-ray crystallography
What is the role of β2-microglobulin in MHC class I molecules?
To pair with the α chain to form the groove
What is the location of the genes that code for MHC class I antigens?
Chromosome 6
What is the function of TCRs and BCRs?
To recognize and bind to antigens
What is the function of the α chain in MHC class I antigens?
To form the peptide binding groove
Why do T cells specific for a particular peptide and a particular MHC allele not respond if the same peptide were to be presented by a different MHC molecule?
Because the MHC molecule is not recognized by the T cell
What is the result of the activation of dendritic cells by binding to detection receptors?
Inflammation and activation of the adaptive system
What is the function of adjuvants in vaccines?
To enhance the immune response to a separate antigen
What are the patterns recognized by phagocytic cells?
Lipoproteins and charged molecules or peptides
What is the characteristic of an antigenic molecule?
It can have several antigenic determinants
What determines the species differences in the immune response?
Genetic factors of the recipient animal
What is the result of the interaction between antigens and the adaptive immune system?
Inflammation and activation of the adaptive system
What is the role of phagocytic cells in the immune response?
To recognize and eliminate pathogens
What is the characteristic of antigens that interact with components of the adaptive immune system?
They can bind to T-cell recognition receptors
What is the main function of MHC molecules in the context of antigen recognition by T cells?
To facilitate the interaction between T cells and antigen-presenting cells
What is the term used to describe the recognition of peptide and MHC molecule by T cells?
MHC restriction
Which of the following MHC molecules is responsible for presenting antigens to CD4+ T cells?
MHC class II
What is the location of the genes that code for MHC class I and class II molecules?
Chromosome 6
What is the significance of MHC restriction in the immune response?
It facilitates the interaction between T cells and antigen-presenting cells
Which of the following T cells does not respond to antigen presentation by MHC molecules?
B cells
What is the role of MHC molecules in the context of antigen presentation?
To process and present antigens to T cells
Which of the following MHC molecules is responsible for presenting antigens to CD8+ T cells?
MHC class I
What is the main consequence of MHC restriction in the immune response?
Restriction of the ability of T cells to recognize antigen
Which of the following cell types is restricted to expressing MHC class II molecules?
Dendritic cells, B lymphocytes, macrophages, and some epithelial cells
What is the role of interferon-γ in the expression of MHC class II molecules?
It induces the expression of MHC class II molecules on certain cells
What is the term used to describe the dual recognition of peptide and MHC molecule by T cells?
MHC restriction
What is the importance of MHC restriction in the immune response?
It restricts the ability of T cells to recognize antigen
What is the name of the Nobel Prize winners who discovered MHC restriction?
Peter Doherty and Rolf Zinkernagel
What is the result of the interaction between MHC class I molecules and viral peptides?
Recognition of viral peptides by CD8+ T cells
What is the characteristic of the MHC class II molecules that allows them to bind to peptides?
The presence of a peptide-binding groove
What is the role of the β2m molecule in MHC class I antigens?
It pairs with the α chain to form the groove
What is the characteristic of the peptides that can be tightly bound to a groove in MHC class I antigens?
They are 9-11 amino acids long
What determines the affinity of individual peptide binding to MHC class I antigens?
The nature and shape of the groove
How do MHC class I and class II antigens differ in terms of their chain structure?
MHC class I has one heavy chain, while MHC class II has two
What is the significance of MHC restriction in the immune response?
It enables the recognition of foreign antigens by T-cells
What is the function of the groove produced by the pairing of the two extracellular domains of the α chain?
It binds to viral peptides
What is the name of the technique used to determine the detailed structure of MHC class II antigens?
X-ray crystallography
Where are the genes that code for MHC class I and class II antigens located?
Chromosome 6
Study Notes
MHC Class I Antigens
- MHC class I antigens are composed of a heavy chain (α) and a light chain (β2-microglobulin)
- The heavy chain is divided into three domains: α1, α2, and α3
- The peptide-binding groove is formed by the pairing of the α1 and α2 domains
- The β2-microglobulin chain is paired with the α chain
- The affinity of peptide binding depends on the nature and shape of the groove
MHC Class II Antigens
- MHC class II antigens have two heavy chains: α and β
- Both chains are coded for by genes in the MHC region of chromosome 6
- The detailed structure of MHC class II antigens was determined by X-ray crystallography
- Each chain is made up of domains of about 110 amino acids held together in a loop by a disulphide bond between two cysteine residues
MHC Restriction
- MHC restriction is the process of dual recognition of peptide and MHC molecule
- The MHC molecule restricts the ability of the T cell to recognize antigen
- MHC restriction was recognized by the award of the Nobel Prize in Medicine to Peter Doherty and Rolf Zinkernagel
Class I and Class II Antigen Expression
- Most nucleated cells express class I molecules
- Expression of class II molecules is restricted to a few cell types: dendritic cells, B lymphocytes, activated T cells, macrophages, inflamed vascular endothelium, and some epithelial cells
- Other cells can be induced to express class II molecules under the influence of interferon (IFN)-γ released during inflammation
Antigen Presentation
- Antigens in different intracellular compartments can be captured and presented to CD4+ or CD8+ T cells via different mechanisms
- There are different forms of MHC molecule, including HLA-DP, HLA-DQ, and HLA-DR in humans
MHC Class I Antigens
- MHC class I antigens consist of a heavy chain (α) and a light chain (β2m)
- The heavy chain is made up of three domains (α1, α2, and α3) with a similar structure and amino acid sequence
- The peptide-binding groove is formed by the pairing of the two extracellular domains (α1 and α2) of the α chain
- The affinity of individual peptide binding depends on the nature and shape of the groove
MHC Class II Antigens
- MHC class II antigens have two heavy chains (α and β) coded for by genes in the MHC region of chromosome 6
- Each chain is made up of domains of about 110 amino acids held together in a loop by a disulphide bond between two cysteine residues
- The heavy chains determine the isotype of the immunoglobulin
- MHC class II antigens have a folded structure with a peptide-binding groove between the α and β chains
MHC Restriction
- MHC restriction is the process of dual recognition of peptide and MHC molecule by T cells
- The MHC molecule restricts the ability of the T cell to recognize antigen
- MHC restriction is important in the immune response and was recognized by the Nobel Prize in Medicine
Expression of MHC Molecules
- Most nucleated cells express class I molecules
- Expression of class II molecules is restricted to a few cell types: dendritic cells, B lymphocytes, activated T cells, macrophages, inflamed vascular endothelium, and some epithelial cells
- Other cells can be induced to express class II molecules under the influence of interferon (IFN)-γ released during inflammation
HLA Loci
- In humans, there are three groups of variable class II antigens: HLA-DP, HLA-DQ, and HLA-DR
MHC Class I Antigens
- MHC class I antigens have a groove produced by the pairing of the two extracellular domains (α1 and α2) of the α chain.
- A peptide of 9 amino acids can be tightly bound to this groove.
- The affinity of individual peptide binding depends on the nature and shape of the groove.
MHC Class II Antigens
- MHC class II antigens have two heavy chains, α and β, both coded for by genes in the MHC region of chromosome 6.
- The detailed structure of MHC class II antigens has a folded structure similar to class I antigens with the peptide-binding groove found between the α and β chains.
- Expression of class II molecules is restricted to a few cell types: dendritic cells, B lymphocytes, activated T cells, macrophages, inflamed vascular endothelium, and some epithelial cells.
MHC Restriction
- MHC restriction refers to the process of dual recognition of peptide and MHC molecule, restricting the ability of the T cell to recognize antigen.
- This process was recognized by the award of the Nobel Prize in Medicine to Peter Doherty and Rolf Zinkernagel.
Immunoglobulin Structure
- Immunoglobulin molecules have a basic structure consisting of two heavy chains and two light chains.
- Each chain is made up of domains of about 110 amino acids held together in a loop by a disulphide bond between two cysteine residues in the chain.
- The heavy chains determine the isotype of the immunoglobulin.
Antigen Presentation
- Antigens in different intracellular compartments can be captured and presented to CD4+ or CD8+ T cells through different mechanisms.
- This process involves the complexing of viral antigen with MHC class I molecules in the endoplasmic reticulum and the complexing of processed exogenous antigen with MHC class II molecules in the endosome.
Antigen Presentation
- Exogenous antigens are processed by the lysosomal route and presented by MHC class II antigens to CD4+ T cells.
- MHC class II molecules are synthesized and stored in the endoplasmic reticulum until they are ready to be transported to the cell surface.
- In the endoplasmic reticulum, class II molecules are prevented from binding to peptides in the lumen by a protein known as MHC class II-associated invariant chain.
MHC Class I and II Molecules
- MHC class I molecules present endogenous/viral antigens to CD8+ T cells.
- MHC class II molecules present exogenous antigens to CD4+ T cells.
- MHC class I molecules are made up of an α heavy chain, controlled by a gene in the relevant MHC locus, associated with a smaller chain called β2-microglobulin, controlled by a gene on chromosome 12.
T-Cells and B-Cells
- T cells specific for a particular peptide and a particular MHC allele will not respond if the same peptide were to be presented by a different MHC molecule or as a different peptide.
- B cells have surface-bound immunoglobulin molecules that can be secreted as soluble molecules, with predetermined specificity for epitopes, and are extremely diverse.
Immunoglobulin Molecule Structure
- The basic structure of the immunoglobulin molecule has a four-chain structure: two identical heavy (H) chains (mol. wt. 50 kDa) and two identical light (L) chains (mol. wt. 25 kDa).
Adjuvants and Immune Response
- Adjuvants are substances that improve an immune response to a separate, often rather weak, antigen.
- Genetic factors, such as species differences and individual differences, can affect the immune response.
- Activation of dendritic cells by binding to detection receptors leads to inflammation and subsequently activates the adaptive system.
MHC Molecules
- MHC molecules have a peptide-binding groove, similar to class I antigens, and are composed of α and β chains.
- The β2-microglobulin (β2m) is a carbohydrate side chain found between the α and β chains.
MHC Restriction
- MHC restriction is the process of dual recognition of peptide and MHC molecule, restricting the ability of T cells to recognize antigens.
- This concept was recognized by the award of the Nobel Prize in Medicine to Peter Doherty and Rolf Zinkernagel.
MHC Class I Antigens
- MHC class I antigens are subdivided into three groups: A, B, and C, each controlled by a different gene locus.
- MHC class I antigens are expressed by most nucleated cells.
MHC Class II Antigens
- MHC class II antigens are expressed by a few cell types, including dendritic cells, B lymphocytes, activated T cells, macrophages, and inflamed vascular endothelium.
- MHC class II antigens can be induced to express in other cells under the influence of interferon (IFN)-γ released during inflammation.
- There are three groups of variable class II antigens: HLA-DP, HLA-DQ, and HLA-DR.
Antigen Presentation
- Antigens in different intracellular compartments can be captured and presented to CD4+ or CD8+ T cells through different mechanisms.
- MHC class II antigens have two heavy chains, α and β, both coded for by genes in the MHC region of chromosome 6.
This quiz covers the biochemistry of protein structure, including the binding of amino acids to a groove produced by beta 2 microglobulin (β2m).
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