Lecture 8: Major Histocompatibility Complex Flashcards
T cells only recognize antigens displayed by ______
MHC complexes on cell surfaces
alpha:beta cells recognize antigens as _______
peptide:MHC complexes
What to MAIT cells and y: gamma cells recognize?
different types of surface molecules whose expression may indicate infection or cellular stress.
What can peptide:MHC complexes signal?
the presence of an intracellular pathogen for elimination by armed effector T cells
What happens in dendritic cells?
peptide:MHC complexes serve to activate antigen specific effector T cells
What does the structure of the TCR/peptide/MHC complexes look like?
APC > MHC> Antigen> Variable Regions on the end with J alpha and Beta chains in the middle> then connected to the C alpha and beta region> then going to the T cell
T Cell receptors recognize antigens in the form of________
a foreign peptide bound to an MHC molecule.
What is the Structure of MHC 1:
-3 alpha chains: 2 on the left, 1 on the right which sits above the B2 microglobulin
What does MHC 2 structure look like?
2 beta chains on the left and 2 alpha chains on the left.
What are the four noncovalent forces involved with MHC?
- Electrostatic Forces
- Hydren Bonds
- Van der Waals forces
- Hydrophobic forces
What are the differences between the distinct subunit compositions of MHC1 and MHC2
MHC1: alpha subunits and closed clefts, ranges from 8-10 amino acids, epitopes in antigen are smaller
MHC2: clefts are open so they are longer peptides
MHC 1 binds ______ by both_____
short peptides 8-10 amino acids, both ends
Peptides bind to MHC molecules through_____
structurally related anchor residues
What is the point of the anchor residues?
They allow for peptide binding stability and specificity of the peptide binding
The length of the peptides bound by MHC Class 2 are ______
not constrained, meaning it is much longer
Peptides that bind MHC class2 molecules are _______ and their anchor residues lie at _________ from the ends of _____
variable in length, various distances, peptides
MHC 2’s variability in length is referred to as ______
open hanging characteristics
- not in the pocket but still involved with receptor interactions
What is unique about the dendritic cell?
It is a supercell and is uber presenting
Cells become targets of T-cell recognition by ______
acquiring antigens from either the cytosolic or the vesicular compartments
Cytosolic Pathogens:
Degrades in: cytosol
Peptides bind to: MHC class 1
Presented to: effector CD8 T cells
Effect on presenting cell: cell death
Intravesicular pathogens:
Degrades: endocytic vesicles (low pH)
Peptides bind to: MHC class II
Presented to: Effector CD4 T cells
Effect on presenting cell: activation to kill intravesicular bacteria and parasites
Extracellular pathogens and toxins:
Degraded in: endocytic vesicles (low pH)
Peptides bind to: MHC Class II
Presented to: Effector CD4 T cells
Effect on presenting cell: activation of B cells to secrete Ig to eliminate extracellular bacteria/toxins
Newly synthesized MHC 1 molecules are retained in _________ until they bind a peptide
the endoplasmic reticulum
How is MHC able to exit the ER and go to the cell membrane?
- Partly fold MHC class I alpha chains bind to __________
calnexin until B2 microglobulins binds
How is MHC able to exit the ER and go to the cell membrane?
- MHC class 1____ complex is released from calnexin, binds a complex of _______ and binds to TAP via tapasin
alpha:b2M complex, chaperone proteins
- Cytosolic proteins and defective ribosomal products are ________ by the proteasome. TAP delivers _______
degraded to peptide fragments, peptides to the ER.
- A peptide binds the MHC class 1 molecules and completes its ______. The MHC Class 1 molecules is released from _______ and exported to ______
folding, the TAP complex, the cell membrane
Peptides that bind to MHC II molecules are generated in __________
acidified endocytic vesicles
Step 1 of MHC2 generation:
1. Antigen is taken up from _______ to _______
extracellular spaces into intracellular vesicles
Step 2 of MHC generation:
2. In early endosomes of neutral pH, endosomal ________
proteases are inactive
Step 3 of MHC generation:
3.______ of vesicles actives proteases to degrade antigen into _______ peptide fragments
Acidification, peptide fragments
Step 4 of MHC generation:
4. Vesicles containing _____ fuse with vesicles containing ______
peptides, MHC class 2 molecules
The invariant chain is ______ CLIP bound to the MHC class II molecules
cleaved to leave a peptide fragment
Cleavage steps of invariate chain
1. invariant chain (Ii) binds in the ______ of MHC II molecules
grooves
- II is cleaved initially to leave a fragment bound to the ___________
class II molecule and to the membrane
Further cleavage leaves a short peptide fragment, _____ to the class II molecules
CLIP
MHC Class II molecules are loaded with _________
peptide in a late endosomal compartment
LAMP______
not in the lysosyme and upregulated
What does an Adaptor Proteins do?
vesicle formation, cargo selection and sorting
Many ______involved in antigen processing and presentation are encoded by _____within the MHC
proteins, genes
The protein products of MHC Class I and class II genes are ____________
highly polymorphic
MHC polymorphism extends the _________ to which the immune system can reponsd
range of antigens: polymorphism, polygeny,
MHC polymorphism affects __________ by T cells influencing both _______and the contacts between _________
antigen recognition, peptide binding, t-cell receptor and MHC molecule
The ______ structures of several peptide:MHC:T-cell receptor complexes show a similar orientation of the T cell-receptor over the ________
crystal, peptide:MHC complex
Why is there a huge variety of HLA?
They can group together on an internal chain and bind to specific peptides.
MHC polymorphism affects ______ by T cells by influencing both peptide binding and the contacts between T_____
antigen recognition, T-cell receptor and MHC molecule
Alloreactive cells recognizing _______ are very abundant
non-self MHC
The CD4 and CD8 cell-surface proteins of T cells are required to ______________
make an effective response to antigen
MHC Class 2 has a ______ interaction with Cd4
beta chain
MHC class 1 has a ______ interaction with CD8
alpha chain
The _____ family of MHC class 1-like molecules is encoded outside the ______ and presents microbial lipids to ________
CD1, MHC, CD1-restricted T cells
The CD1 family of MHC class 1-like molecules is encoded outside ______ and presents microbial lipids to _________
the MHC
CD1-restricted T cells
Which MHC class molecule is more restricted?
MHC2
Dendritic cells are expressed on which classes?
both MHC1 and MHC2
B cells are expressed on which classes?
MHC class 1 and 2
T cells are expressed more on ____
MHC class 1
Neutrophils are expressed on _____
MHC class 1
What other nucleated cells are expressed on MHC class 1
hepatocytes, kidney, and brain
