MHC Polymorphisms and Functions Flashcards
What are the roles of the subunits found in proteosomes?
They insure that the peptide is 8 to 10 aa long
A mutation in which protein will cause anergy?
B7
What three cell types are classified as professional antigen presenting cells?
Dendritic cells
Macrophages
B lymphocytes.
How are CD1 molecules unique?
They share structural similarities with classical MHC I but are functionally similar to MHC II
What needs to happen before an antigen can be presented to a T cell?
It must be processed first
Various types of T cells (expressing_____________receptors , can react against __________ antigens, such as mycolic acid, derived from well-known pathogens, such a ______________
gamma Delta ; lipid; Mycobacterium tuberculosis .
Immunoflurescent labeling
used to determine importances of the trimeric protein, CD74, in transporting the MHC II molecule out of the rER
HIV progression is associated with which susceptibility allele? Which protective allele? Which population?
B35; A1-B8-DR3
B27
USA, EUROPE
Cells that display peptides associated with class I MHC molecules to CD8+ Tc cells are referred to as target cells____________.
Cells that display peptides associated with class II MHC molecules to CD4 + TH cells are called ____________
Target cells
antigen-presenting cells (APCs).
Peptides assemble with class II MHC molecules by displacing____________
CLIP
Which enzymes are found in lysosomes?
Proteases
Nucleases
Glucosidases
Lipases
Phospholipases
Phosphatase
How do professional antigen presenting cells differ from each other?
In their mechanisms of :
- Antigen uptake
- Whether they constitutively express class II MHC molecules.
- In their costimulatory activity
How are macrophages activated?
By phagocytosis of particulate antigens before they express class II MHC molecules or by costimulatory membrane molecules such as B7.
Which cells are the most effective antigen presenting cells? Why?
Dendritic cells because they constitutively express a high level of class II MHC molecules, they have costimulatory signals, and they can activate naive TH cells
What is CLIP?
It is a small part of the trimeric protein that rest directly in the peptide binding cleft preventing the binding of endogenous antigens.
B cells internalize antigen very effectively by ____________ using antigen-specific membrane antibody as the receptor.
receptor mediated endocytosis
Classical genes on MHC
HLA-A, HLA-B, HLA-C
What role does pH play in peptide binding?
A neutral pH allows for the disassembly of the CLIP- cleft complex, which allows for a peptide to fully bind to the complex. A neutral pH is found on the surface of the membrane
Tuberculosis is associated with which susceptibility allele? Which protective allele? Which population?
DR2
N/A
India, Russia, Indonesia
A nonclassical class II MHC molecule called _________ is required to catalyze the exchange of CLIP with antigenic peptides.
HLA-DM
Which professional antigen presenting cell can cross present?
Dendritic cells
Alleles found in MHC molecules differ by individual by _____ to _______%.
5; 10
How are endogenous antigens eliminated?
They are processed in the cytosolic pathway (peptide is ubiquitinated and then broken down by the cytosolic protease complex, it is then sent to the endoplasmic reticulum via TAP proteins, and lastly it binds to the MHC I molecule). The peptide-MHC I complex go to the surface of the membrane
What is the role of the trimeric protein in MHC II processing and transport?
- interacts with the peptide binding cleft
- Prevents any endogenously derived peptides from binding to the cleft while the class II molecule is within the RER
- Incolved in the folding of the class II alpha and beta chains
- Helps to guide the CLASS II alpha and beta chains exit from the rER, and the subsequent routing to the enocytic processing pathway
To ubiquinate something, you need a lot of __________ to add the UQ proteins, this
destines them for _________
ATP;degradation.
What is the most variable region on the MHC I molecule?
Regions a1 and a2 because they are the regions that bing the antigen
What 3 compartments does the endolytic pathway contain?
- Early endosome (ph 6-6.5)
- Late endosome (pH 5-5.5)
- Lysosome (pH 4-4.5)
What are the subunits of the proteosomes that degraded endogenous antigens?
LMP2, LMP7, LMP10
Hepatitis B persistence is associated with which susceptibility allele? Which protective allele? Which population?
n/a
DRB1*1302
Gambia, Germany
Leprosy is associated with which susceptibility allele? Which protective allele? Which population?
DR2
N/A
India
What is the most variable region of the MHC II molecule?
B1 and a1, as they bind the antigen
The presence of what factor indicates whether or not a T cell has been activated?
Interleukin 2
Nonpeptide antigens are presented by members of the __________family of nonclassical class I molecules.
CD1
Assembly and stabilization of MHC I molecules
- Calnexin binds the MHC I alpha chain, which allows the Beta2 globulin chain to bind to the alpha chain.
- Calnexin is released
- Tapasin, Calrecticulin, and ERp57 bind to the MHC I molecule, which stabilizes it so that a peptide can bind.
- Once the peptide binds, Tapasin, Calrecticulin, and ERp57 disassemble from the complex.
- The MHC I- peptide complex is now ready to leave the rER.
An increase in systemic lupus erythematosus is associated with which HLA allele?
DR3
How are B cells activated? What is their relationship with MHC II molecules?
B cells constitutively express MHC II but they must be activated before they can express costimulatory molecules.
Hepatitis C persistence is associated with which susceptibility allele? Which protective allele? Which population?
n/a
DR5
Italy, UK
- 1 gene per __________ kilobases
- ___________loci with _________predicted to be expressed
- ______% of expressed genes have immune function
- Class I and II have over _________allelic variants
16; 224 ; 128 ; 40; 1678
How are exogenous antigens eliminated?
Antigen is endocytosed or phagocytosed and then broken down by lysosomes. The antigen then binds to the MHC II molecules. The MHC II- peptide complex then go to the surface of the membrane
Malaria is associated with which susceptibility allele? Which protective allele? Which population?
B53
DRB1*1302
Gambia
What is cross-presentation?
The ability of dendritic cells to take up extracellular pathogens and present them to cytotoxic T cells. This then activates these T cells
What protein in responsible for guiding the MHC II molecule to endolytic vesicles?
Trimeric protein, The invariant chain (CD74)
An increased risk in some autoimmune diseases is associated with what HLA alleles? Which autoimmune disease?
B27
Ankylosing spondylitis
Reactive arthritis
Reiter’s Syndrome
An increase in insulin-dependent diabetes mellitus is associated with which HLA allele?
DR4/DR3
What are the distinguishing features of antigen-presenting cells?
- Their ability to express class II MHC molecules.
- Deliver a costimulatory signal.
