Antigen presentation Flashcards
Which chromosome encodes MHC proteins?
Chromosome 6
What are MHC proteins called in humans?
HLA (huma leukocyte antigens) proteins
What is the MHC haplotype?
the total set of MHC genes (D region genes and A, B, and C genes) on each chromosome.
What is MHC polygenic
Because an individual inherits one haplotype from each parent, and is thus comprised of many different genes within an individual
What makes MHC gene expression polymorphic?
Multiple variants of each gene exist in the population as a whole
True or false: MHC genes are by far the most polymorphic genes known in humans.
True
What is the system that distinguishes different HLA protiens within a given gene family?
The number tagged onto the end ot the HLA type (example: HLA-A3 or HLA-A15).
What does it mead to say that MHC genes codominant?
alleles on both chromosomes will be expressed simultaneously
Which region on DNA encodes for class II MHC proteins?
D regions
Which region on DNA codes for class I MHC proteins?
A, B, and C genes
How many MHC genes do we receive from each parent?
3 from each parent
How many MHC genes are expressed by an individual?
6 total, but may be more higher because some class II MHC α and β proteins (which compose each class II MHC protein) can pair up with other class II MHC α and β proteins to produce new α/β chain combinations
What three characteristics of MHC genes virtually guarantees that no two individuals (save twins or siblings) will have the same MHC genes?
The polygenic, polymorphic and codominant characteristics
What is the function of MHC proteins?
Present antigens to T cells
True or false: T cells can generate a response without the help of an MHC cell
False (“need to be spoon-fed”)
What sort of bond exists between peptides and MHC proteins on the cell surface?
Non-covalent
True or false: there is no bonding between MHC cells and T cells, only the antigen connect them
False
What is the purpose of T cells not being able to bind to antigen directly?
Localizes to anatomic site of antigen presentation
True of false: MHC cells can bind to antigens that are not proteins
False
What disease is associated with narcolepsy?
HLA-DR2
What disease is associated with HLA-B27?
Ankylosing spondylitis
What is the immune response theory of the HLA gene association with diseases?
Some individuals are unresponsive to certain pathogens because that antigen cannot be bound to that particular individual’s HLA proteins.
What is the altered self hypothesis of the HLA gene association with diseases?
The disease agent alters molecules of an individual’s body such that the immune system now recognizes it as foreign when it binds to certain HLA proteins.
Why might the associated of HLA genes and various diseases have no causative connection to one another?
May just be in close proximity to diseased allele, and thus usually inherited together
What are the two clinical uses of MHC typing?
Organ transplant
Paternity testing
Why is MHC matching important in organ transplant?
of organs between individuals may be rejected since a non-self MHC protein will be recognized as foreign.
Can paternity tests done via HLA haplotypes 100% rule out a father? Can they 100% rule in?
Can rule out 100% but cannot rule in 100%
Which class of MHC proteins are expressed on nearly all nucleated cells? Which cell type does not express it?
Type I
Corneal epithelium and RBCs
Why does Plasmodium, the causative agent in malaria, go undetected by T cells?
RBCs do not have MHC class I
What are the two chains in class I MHC proteins? Which one forms the binding site for antigens?
Alpha and beta, with alpha forming the binding site
What are the four regions of class I MHC proteins?
- peptide-binding region
- immunoglobulin-like region
- transmembrane region 4. cytoplasmic region.
The beta portion of the class I MHC protein does not bind to antigen. What, then, is its function?
The beta2 microglobulin is required to keep the proper conformation and cellular expression of the beta chain.
Which CD lymphocyte binds to MHC class I?
CD8+T
How large of a peptide can class I MHC proteins bind?
9-11 amino acids
Since class I MHC can hold only small peptides, intact protein antigens cannot bind to the MHC protein. What must occur for the antigen to be presented to T cells?
processing of the antigen into small fragments must occur.
Where does polymorphisms occur withing the MHC class I protein? What is the consequence of this?
in the -helices that compose the sides of the cleft and the -pleated sheets that make up the floor of the cleft
therefore certain MHC class I alleles may bind certain peptides better than others.
On what cells are class II MHC molecules expressed?
Dendritic cells
Macrophages
B lymphocytes
(Thymus can too)
What protein induces the expression of class II MHC proteins on cells that don’t normally express them?
Interferon-γ
What are the two proteins fragments that make up MHC clas II molecules?
Alpha and Beta (each 205 amino acids long)
True or false: Each MHC protein is encoded for by a separate MHC gene.
False– Each chain is encoded for by a separate MHC gene.
What are the four regions of class II MHC proteins?
- a peptide-binding region
- immunoglobulin-like region
- transmembrane region
- cytoplasmic region
Which T lymphocytes utilize class II MHC proteins?
CD4+ T lymphocytes
How large of proteins can class II MHC proteins hold?
10-30 amino acids, but can have “hot-dog” ends to allow for longer polypeptides
Polymorphism among class II MHC proteins occurs where?
in the antigen-binding cleft
What are the MHC restrictions?
The fact that:
CD4+ binds MHC class II
CD8+ binds MHC class I
What must happen for T-lymphocytes to recognize proteins of antigens?
Proteins must be denatured, and presented in a linear form
Why can B lymphocytes recognize antigens directly, whilst T lymphocytes must utilize MHC proteins?
B lymphocytes can bind directly to conformational, or linear sequences of proteins, whereas T lymphocytes need to have denatured, linear proteins
Why can’t T lymphocytes recognize non-protein antigens?
because these substances cannot be processed in such a way as to generate fragments that can bind to MHC proteins
What is the significance of the fact that class I MHCs can be expressed by nearly all nucleated cells?
Serves to make binding sites for CTLs
What are the most potent antigen presenting cells, and are the best in presenting antigens in the primary immune response?
Dendritic cells
What are macrophages better at stimulating than dendritic cells?
Secondary immune response
Where are Dendritic cells produced?
Bone marrow
Which cells continuously sample their environment through phagocytosis and macropinocytosis?
Dendritic cells
True or false: dendritic cells are only found in parts of the body that are exposed to antigens frequently
False–they are everywhere, always.
Macrophages tend to present antigens from where?
Pathogens
B lymphocytes tend to present what type of antigens?
Soluble ones
Why do dendritic cells and macrophages have an advantage over B lymphocytes in the number of different protein antigens they can process and present?
because these cells contain more proteases with which to process antigens, and they are found constitutively in high concentrations
Why can B lymphocytes bind and process antigen that is present in far less concentration, than can macrophages?
More specific antigen binding domains
What is the function of gamma interferon? What cells produce it, and what cells react to it?
T lymphocytes produce it after they have been brought an antigen. This causes antigen presenting cells to produce higher levels of class II MHC proteins, and epithelial surfaces to produce it.
What are the two overall effects of gamma interferon production by T lymphocytes?
- to provide more cells to present antigen to T lymphocytes
2. higher levels of class II MHC expression on the antigen-presenting cells.
True or false: gamma interferon can enhance class I MHC protein presentation on cells types, along with the main effect of increasing class II MHC production?
True
What happens to dendritic cells when they encounter an antigen, and mature?
lose their ability to phagocytize
Where do dendritic cells go once they encounter an antigen?
Lymph nodes
What are the three ways that exogenous antigens are internalized in the class II MHC antigen processing pathway?
- Phagocytosis
- Receptor mediated endocytosis
- Fluid phase pinocytosis
What is the time frame for antigen processing via class II MHC?
1-3 hours
Class II MHC proteins are bound by what, so that they cannot bind the cell’s own newly synthesized proteins
MHC class II-associated invariant chain (the cork thingy)
What are the two proteases needed in the class II MHC antigen processing pathway?
cathepsins S and L
In cells that are not processing antigen, what binds to class I MHC proteins?
Self proteins
Through what pathway are endogenous antigens processed?
Class I MHC processing pathway
True or false: the polypeptide sequence of a given antigen determines whether it will be processed via the class I or II pathway
False–only where they are found in the cell
What is the first step in cytosolic protein antigen processing?
Breakdown via proteasome
What happens after proteosomes break down endogenous antigens into smaller proteins?
Peptides are transported to the endoplasmic reticulum by TAP
What is the heterodimer protein that transports peptide fragments from the cytosol to the ER after they have been degraded by proteosomes in the Class I antigen presenting pathway?
TAP (1 &2)
What induces the TAP proteins and the peoteasomes involved in the class I antigen presenting pathway that increases their activity during a viral infection?
Interferons
What happens after Peptide-class I MHC complexes are formed in the ER, in the class I antigen presenting pathway?
these complexes are shuttled out to the plasma membrane of the virally-infected cell to alert T lymphocytes that the cell is infected
True or false: Class I MHC proteins are not released from the endoplasmic reticulum until first bound with peptide.
True
What determines the immunogenicity of antigens?
Their ability to bind MHC molecues (maybe)
Exogenous antigens are processed via which pathway?
Class II MHC proteins
Endogenous antigens are processed through which pathway?
Class I MHC proteins
Which pathway (class I or II) are involved in fighting CA?
class I MHC
How do dendritic cells pass exogenous antigens into the class I MHC pathway?
This process involves the fusion of phagosomes containing the exogenous antigen with the endoplasmic reticulum (then go through path I)
