Exam 2 - T Cells - Receptors, MHC, and Antigen Recognition Flashcards
What is the main function of CD8 T cells?
Kill virus-infected cells
What is the function of CD4 T1 cells?
Activate infected macrophages
Provide help to B cells for antibody production
EXTRACELLULAR BACTERIA
What is the function of CD4 T2 cells?
Provide help for B cells for antibody production, esp switching to IgE
Helminth parasites
What is the function of CD4 T17 cells?
Enhance PMN response
PROMOTE BARRIER INTEGRITY - MUCOSAL SURFACES
What is the fx of all types of T cells?
B cell help
Isotype switching
Antibody production
What is the fx of CD4 regulatory T cells?
Suppress T cell responses
What do TCRs (T Cell Receptor) bind?
Polypeptides
Where are TCRs expressed?
On cell surfaces, never secreted
Similar in structure to immunoglobulins
Interacts with MHC presented antigen
What are the 2 classes of TCRs?
Alpha:Beta T Cells
Gamma:Delta T Cells
Tell me about Alpha:Beta T Cells.
- Develop and mature in the thymus
- “Classic” T cell
- Adaptive immunity
- Common in CIRCULATION, not tissues
- Positive and negative selection
Tell me about Gamma:Delta T Cells.
- Not involved in adaptive immunity
- Monitor tissue health
- Common in TISSUES, not circulation
- DEVELOPS, but does not mature in the thymus
- Limited positive and negative selection
T/F - T cells only express one type of TCR class, NEVER both.
TRUE
CD4 T1 take care of what?
CD4 T2 take care of what?
CD4 T17 take care of what?
T1 - Small, extracellular
T2 - Big, multicellular
T17 - Mucosal
T/F - TCR genes undergo rearrangement.
TRUE
The alpha chain has what segments on it?
V, J, and C segments with junctional diversity
V = Variable J = Junctional C = Constant
The beta chain has what segments?
V, J, D, and C segments with junctional diversity
D = Diversity
TCRs req the ______ complex for signal transduction.
CD3
It mediates TCR signaling, and expression does NOT occur w/o CD3
What fragment is the TCR associated with in signal transduction?
Zeta fragment
What does MHC stand for?
Major histocompatibility complex
What are the two classes of MHC?
I
II
What antigen does MHC class I target and what cells have MHC I?
Intracellular antigen
Nearly all cells have it
What parts make up the MHC class I?
Alpha chain (alpha 1,2, and 3)
Beta 2 microglobulin
What type of antigen loading happens with MHC class I?
ER antigen loading
CD__ communicates with MHC Class __, while CD__ communicates with MHC Class __.
CD8 - MHC Class I
CD4 - MHC Class II
MHC Class II targets when antigen type and what cells have MHC II?
Internalized antigen
Antigen presenting cells
- B cells
- Macrophages
- Dendritic cells
What chains are in MHC Class II?
Alpha and beta chains
Which type of antigen loading does MHC II do?
Vesicular ER loading
CD8 receptor binds which domain on MHC Class I?
Alpha3
The CD4 receptor binds what domain on the MHC II molecule?
Beta chain
What does the beta 2 microglobulin do for the MHC Class I molecule?
Stabilizes the molecule
In general, both MHCs do what?
Bind peptides for TCR presentation
They are promiscuous, not particular at all
Nearly all cells express some form of MHC
-RBCs are devoid of MHC
The following are hematopoietic cells. Which are MHC I and which are MHC II?
T cells B cells Macrophages Dendritic cells Neutrophils Erythrocytes
T cells - I
B cells - I and II
Macrophages - I and II
Dendritic cells - I and II
Neutrophils - I
RBCs - NONE
The following are non-hematopoietic cells and they all express what type of MHC Class?
Hepatocytes
Kidney epithelium
Brain
MHC Class I
Tell me the process of MHC Class I antigen presentation.
Intracellular antigen
Proteasome - Antigen broken down to peptides here
Peptides transported to ER
Peptide bound by MHC Class I
MHC Class I present peptide at cell surface
Tell me the MHC Class II antigen presentation.
Extracellular antigen
Endocytosis vesicle
Peptides produced in phagolysosome
MHC Class II comes vesicled from ER and meets with phagolysosome
Peptides are bound to MHC Class II w/in phagolysosome
MHC Class II presents peptide at cell surface
Tell me the detailed version of MHC I antigen loading in the ER.
MHC Class I heavy chain is stabilized by CALNEXIN until beta2-microglobulin binds
CALNEXIN is released and a complex of calreticulin, tapasin, ERp57, and TAP forms.
A peptide is delivered by TAP to the heavy chain - this forms the “mature” MHC Class I molecule
MHC Class I dissociates from the complex and is exported from the ER to the cellular surface
MHC I - Antigen Loading in the ER allows for what?
Peptides trimmed before expression
Allows detection of intracellular infection
Intracellular peptides are 8-10 residues
T/F - Crosspresentation of endocytosed antigen is just that internalized antigen is expressed on MHC Class I and MHC Class II.
TRUE
This is important in naive CD8 T cell activation
Tell me the detailed version of MHC II - Antigen Loading into vesicles.
Antigen is taken from the extracellular space into intracellular vesicles
Early endosomes have neutral pH, and endosomal proteases are inactive
Acidification of vesicles activates proteases to degrade antigen into peptide fragments
Vesicles containing peptides fuse with vesicles containing MHC Class II molecules
What prevents self antigen presentation?
CLIP
Tell me the detailed version of what CLIP does.
INVARIANT CHAIN blocks binding of peptides to MHC Class II in ER
Invariant chain is cleaved off in vesicles, but the CLIP portion of the invariant chain remains bound
CLIP blocks binding of peptides to MHC Class II
HLA-DM facilitates release of CLIP, and peptides bind
What is CLIP?
Class II-associated invariant chain peptide
What dictates MHC specificity?
Co-receptors
*This is within the T Cell Synapse
What happens when a CD8 T cell contacts a virus infected cell?
It leads to apoptosis
What happens when a CD4 T cell contacts a macrophage?
Cytokines released and those activate a macrophage to release their own cytokines
What happens when CD4 T cells contact B cells?
Cytokines are released and B cells differentiate into plasma cells, and then antibodies are released from the plasma cell