Adaptive immunity- antigen processing and presentation, dr. hudson Flashcards
In a viral infection, _ made by b cells can neutralize extracellular virus particles, but the source of the virus must be eliminated by _
antibodies, the humoral (b cell) response
T cells
An effective immune system has to devise a system to sample both the _ and _ compartments.
vacuolar (injested bacterial material), cytoplasmic (where viruses would put their product protein)
Peptide fragments are “presented” to T cells on _ molecules in a process called _ _
Class 1 or class 2 MHC
antigen presentation
Outside of the cell is sampled by class _ MHC, inside of a cell (cytoplasm) is sampled by class _ MHC
outside- class 2, inside, class 1
Concepts underlying class 1 MHC antigen presentation to T cells
- proteins must be _ _ _
- _ must occur to generate peptides of the appopriate size
- peptides must be _ to class 1 MHC molecules
- Peptides must _ to class 1 MHC molecules
- Peptides must be displayed to _ in the contect of class 1 MHC molecules
tagged for destruction
proteolysis
delivered
bind
T cells
Small molecule (8kDa) added to lysine residues on proteins destined for degradation.
ubiquitin
What kinds of peptides are presented on class 1 MHC molecules?
all were 9 peptides in length, ending in a hydrophobic (valine or isoleucine)
3 types of protease activity associated with the proteosome. Caspase-like, trypsin-like, and chymotrypsin like. Chymotrypsin like cleaves after _ amino acids
hydrophobic
a protective cytokine usually associated with a virus infection
upregulates proteosome subunits called LMPs, which increase production of peptides suitable for antigen presentation (chymotrypsin activity)
IFNγ
(interferon gamma)
–>immunoproteosome
Proteosome cap recognizes and removes_, but then the protein must be _ to go into the proteosome, which is located in the cytoplasm.
Peptides from the proteosome go into the ER via the _ transporter and bind to the newly synthesized _
ubiquitin chain
unfolded
TAP (Transporter associated with Antigen Processing)
Class 1 MHC molecule
TAP
Encoded in _ gene
_ membrane spanning domain integral membrane proteins
One substrate: _, ending with _ _ _ _ are favored
Size range: _-_ amino acid residues
MHC (major histocompatibility complex) on chromosome 6
12
peptides ending with L I V M are favored
6-15
Class 1 MHC molecule has size restriction, it accepts residues that are _-_ residues long
The Class 1 MHC assembles with a light chain called _
Loading complex includes _ molecule which is thought to tether the newly synthesized class 1 MHC molecule to TAP, keeping it in close proximity to incoming peptides
8-10
B2m (beta2 microglobulin)
tapasin
T cell receptors (TCR) recognize the combination of _ + _
MHC + peptide
“Education” of T cells in the thymus occurs during development.
Which types of t cells die and which do not?
The t cell that recognizes self peptide and mhc complex with high affinity dies, the t cell that does not have any affinity dies (death by neglect)
Weak/moderate affinity T cell receptors live to populate the periphery
What is alloreactivity
the reactivity of T cells (or B cells) to non-self (allogenic) MHC class 1 or 2 molecules.
The ones that went to live on after thymic education had weak affinity, but if they come across foreign peptides inside of a self MHC or a foreign MHC (from translant) then the T cell will kill the target cell.
This is the reason for immediate transplant rejection
Structure of class 1 MHC?
What is the “light chain”
What is the “heavy chain?
Where does the peptide sit?
What is the difference between Class 1 and Class 2 MC in structure?
B2m
a1,a2, a3
Between a1 and a2
class 2 has two heavy chains and is encoded by two genes. Alpha chain and Beta chain. The class 1 MHC is coded by one gene.
Class 1 peptides are _-_ residues
Class 2 peptides are _-_ residues, can be longer
8-10
10-16, can be up to 30
Some differences between class 1 and class 2 pressentation to T cells.
Which one needs to tag proteins for destruction?
Which class is used for engulfed pathogens?
Which class must have peptides delivered to it?
Class 1 MHC, these are for the inside of the cell
Class 2 MHC is used for englufed
Class 1, using the TAP
Which class of MHC…. peptides must be displayed to *CD8 T CELLS* in the context of MHC molecules?
Which class of MHC… peptides must be displayed to *CD4 T CELLS* in the context of MHC molecules?
Class 1
Class 2
Loading of peptide occurs in the ER for this class of MHC
Loading of peptide occurs in the endocytic compartment for this class of MHC
Class 1
Class 2
Tagging of proteins for destruction happens with this class of MHC
Class 1 MHC
proteolysis for class 2 does not require tagging to the proteosome, but rather requires delivery to the _ where _s at a pH5 will chop them up
where it will also be loaded and displayed to _
Lysosome, antigen undergoes proteolysis into peptides, mediated by lysosomal proteases (cathepsins)
CD4 T cells
Class 2 molecules are made in the ER (like class 1) but they do not bind peptides there because of _
Invariant chain (Ii)
scaffold, stabilizer to MHC 2
Barrier to peptides in the ER
has “Zip code” to MIIC (LL) (sorting signal)
invariant chain (Ii)
What is the purpose of the invariant chain?
forms a trimer with 3 class 2 MHC molecules and 3 invariant chains.
scaffold, stabilizer to MHC 2
Barrier to peptides in the ER
has “Zip code” to MIIC (LL) (sorting signal)
What happens when Invariant chain and MHC2 trimer gets to the lysosome?
Cleavage by lysosomal enzymes leaves a short peptide fragment, CLIP, bound to the class 2 molecule.
What molecule is responsible for dislodging the CLIP peptide (remnants of invariant chain (Ii) from the class 2 molecule?
HLA-DM
Self peptides (can/cannot) be presented by class 2 molecules
Can, anything targeted to the lysosome. Tissue debris from tissue damage, macrophages engulf self and present these peptides to CD4-t cells
Antigen in the periphery is englufed by _ cells that activate T cells
dendritic cells. They migrate to a lymphoid organ, where naive b and T cells reside. This is where T cells first see the antigen. To activate virus specific CD8+ T cells, in the lymph node, if a particular CD8 T cell can bind tightly to that antigen/ MHC class 1 complex, it becomes activated to proliferate.
If dendritic cell ENGULFS virus, then it will display class _ MHC complex and will interact with CD_+ T cells
If it is INFECTED by virus proteins, it will display class _ and will interact with CD_+ T cells
engulfed- Class 2, Cd4
infected by- Class 1, Cd8
Which cells can have cross presentation to T cells? if it engulfs a virus but isnt infected by a virus, it will present *Class 1* as well as Class 2
dendritic cells, a specialized antigen presenting cell
Describe cross presentation
The specialized antigen-presenting cell’s ability to present Class 1 and class 2
Antigen presentation molecule that is similar to class 1 and class 2 MHC molecules in structure (also has B2m and have similar shaped groove for binding antigen) but instead of peptides they bind lipid antigens.
CD1 molecules
Cd1 molecules bind
lipid antigens
Antigen presenting cells have _, _, and _ expression.
Other cells, like liver cells, only have _
Class 1, 2, CD1
Class 1
CD1 specific T cell that express classical T cell receptors (alpha/beta) and recognize lipid antigens
NK-T cells
Specialized antigen presenting cells (3)
B cells
Dendritic cells
Macrophages
class of MHC molecule expressed on all nucleated cells
MHC 1
class of molecule expressed only on specialized antigen presenting cells
MHC2
MHC 1 molecules present peptides derived from _ proteins to CD_T cells
cytosolic, cd8
mhc 2 molecules present peptides derived from _ proteins to CD_ tcells
intravesicular
4
_ is essential for stable expression of MHC molecules at the cell surface
peptide binding
