Lecture 7: Antigen Presentation and the MHC Flashcards
All nucleated cells express ______ ______ __ molecules and can present antigen via these molecues
MHC Class I
What are 2 methods in which antigen presenting cells can take up antigen?
1) surface receptors
2) phagocytosis
What are the 3 cell types where MHC Class II is expressed?
1) Macrophages
2) Dendritic cells
3) B lymphocytes
What are skin APCs called? Where do they present antigen?
Langerhan cells; T cells
What are the 2 lineages of Dendritic Cells?
1) Conventional
2) Plasmacytoid
What is the function of Plasmacytoid cells?
produce large quantities of interferon in response to viral infections
What are the macrophages in the brain?
microglial
True or false: B lymphocytes present only one type of antigen?
True (whatever binds to B cell receptor)
What is required for the actual presentation of antigens for MHC Class I?
cytosolic production of viral proteins
How do MHC Class II molecules pick up the ingested antigen?
vesicles containing MHC Class II fuse with the vesicle in which the antigen was phagocytosed
Antigenic peptides that bind to MHC Class I are typically derived from ________
viruses
In MHC Class I antigen presentation, peptides generated in the cytoplasm are transported into the ER by ________ and ________.
TAP 1 and TAP 2
transporters associated with antigen processing
Once in the ER, how does the antigenic peptide associate with MHC Class I molecules?
MHC Class I associates with TAP and as peptides are transported into the ER, they are trimmed by ERAAP (endoplasmic reticulum aminopeptidase associated with antigen processing) then bind to MHC Class I
As MHC Class I is being made in the ER, what do the alpha chains post up against while waiting for the beta 2 microglobulin to bind?
calnexin
Once the beta 2 chains associate with the alpha chains of the MHC, what keeps the molecule from unfolding?
binding to chaperone protiens (calreticulin, ERp57)
Which chaperone facilitates MHC Class I binding to TAP?
tapasin
When is the MHC Class I molecule released to the membrane?
Once it has bound to its peptide in the ER (after ERAAP cleaved the incoming antigen)
MHC Class I peptides are degraded in the ____________ while MHC Class II molecules are degraded in _____________.
cytosol (by the proteasome) and acidified endosomes
MHC Class II molecules are transported to endosomes with _____________ which occupies the peptide binding cleft of the newly synthesized MHC
invariant chain (Ii)
Once in the endosome, Ii is cleaved, leaving a short peptide fragment called _______
CLIP
class II associated invariant chain peptide
CLIP is only removed from the binding cleft when the endosome fuses with an phagocytized vesicle of antigen. Which protein unloads CLIP and loads the antigen?
DM
Under normal conditions, MHC Class I molecules are __________(loaded/unloaded) while MHC Class II are ___________
loaded (with self peptides derived from normal degradation)
unloaded (only have CLIP in binding groove)
Under normal conditions, MHC Class I molecules are __________(loaded/unloaded) while MHC Class II are ___________
loaded (with self peptides derived from normal degradation)
unloaded (only have CLIP in binding groove)
CD4 T lymphocytes do not recognize free/soluble antigens, they only recognize ________
MHC Class II bound
What is MHC restriction?
the genetic restriction by class II molecule on which the antigenic determinant was first recognized
What are the 2 potential functions of CD4 cells?
1) mediate macrophage activation
2) act as helper cells in antibody responses (secrete cytokines)
What are the subset of CD4 T cells that activate macrophages?
Th1
What are the subset of CD4 cells that induce antibody synthesis?
Th2 (helpers)
What is the definition of naive T cells?
have never encountered antigen before
Dendritic cells mature when they
phagocytize an antigen
What feature of mature dendritic cells enhance their ability to present antigen?
expression on their surface of large amounts of co-stimulatory molecules (B7) and ability to express lots of cytokines for T cell differentiation and proliferation
What are the 2 signals required for activation of naive T cell?
1) presentation of peptides by MHC (engages with TCR on T cell)
2) interaction between B7 on the APC and CD28 on membrane of the T cell
B7 on the APC interacts with ______ on the T cell
CD28
True or False: all APCs express B7
False
in this case, T cell activation relies on CD40
All T cells that recognize peptides expressed by MHC Class II are stimulated to express _______
CD40L
CD40 ligand
CD40L on the T cell engages ______ on the surface of the APC in order to induce expression of B7
CD40
B7 binding to CD28 results in _________________
enhanced T cell proliferation and differentiation
What process activates B cells to express B7?
displaying process peptides on surface MHC Class II
After B7 of the B cell binds to CD28 on the T cell, what happens?
The T cell is stimulated to express CD40L which then engages CD40 on the surface of the B cell
Once CD40L engages CD40, what happens?
the T cell is activated and produces cytokines and the B cell is free to proliferate and differentiate into plasma cells
Define immunological synapse?
sustained TCR engagement and signaling with MHC peptides
The activation of T cells is mediated by what 2 events
1) interaction of TCRs with their MHC ligands
2) B7 associating with CD28
Ephemeral TCR engagement is sufficient for triggering killer T cells but __ _____ ____________ requires TCR engagement/signaling for many minutes or hours
T cell proliferation
The mature immunological synapse is defined by a pattern of receptor segregation with a central cluster of TCRs surrounded by rind of adhesion molecules like ________
LFA-1
The mature immunological synapse is defined by a pattern of receptor segregation with a central cluster of TCRs surrounded by ring of adhesion molecules like ________
LFA-1
What is the purpose of the ring of adhesion molecules?
promote TCR-MHC-peptide interaction
LFA-1 is on the _______ while ICAM is on the ______
T cell; APC
