Antigen Capture and Presentation to Lymphocytes Flashcards
B cell receptors (BCR) can regonize a variety of macromolecules in soluble form or cell surface associated form, these include…
proteins, polysaccharides, lipids, nucleic acids and haptens
T cell receptors (TCR) can only recognize peptide fragments of protein Ags, only when the peptides are generated in a host cell and presented on to cell surface with specialized molecules called…
major histocompatibility complex (MHC)
T cells protect against intracellular microbes, however, T cells also help to mount a Ab to extracellular pathogens, also known as?
T helper cells
T cells cannot recognize unprocessed Ags, they are processed by…
being broken up into linear peptides and displayed by APCs with MHC molecules on the cell surface
What do CDH4 T helper cells recognize peptides Ags as?
as presented in complex with MHC class II molecules on DCs, Mø, and B cells
CD8 T cells recognize peptides associated with what?
MHC class I (call cytotoxic b/c kill host cells infected with pathogens)
CD4 and CD8 attach differently to non-polymorphic part of the MHC class II and MCH class I respectively. CD4 and CD8 are called co-receptors because..?
They involve signaling/activation
What else needs to be done besides for Ag presentation to the TCR, in order to activate naive T cells?
APCs with CD4 and CD8 express co-stimulatory molecules which are involved in signaling events
What does T cell activation produce, which stimulate clonal expansion of Ag activated T cells?
Cytokine IL-2
Activated Th1 cells produce what, that activates macrophages to rid of intracellular microbes as well as develop cytotoxic T cells?
Th1 produces cytokines
Activated Th2 cells produce what, which is important for B cell proliferation?
Cytokine IL-4
What are the main function of Th2 cells?
help B cells to produce Abs and develop plasma cells (antibody production) and memory cells against extracellular microbes
TCR (T cell receptor) is composed of 2 polypeptide chains alpha and beta with weights of 50 and 39 kDa. Each chain has a constant and variable region like Ig. What do the variable sites of the alpha and beta chains make up?
the Ag-binding site
What happens when T cells have gamma/sigma characteristics instead of alpha/beta?
They have a broader specificity for unconventional Ags
T cells expressing CD4 bind to the nonpolymorphic region of MHC class II on APCs restricting Th cells to recognize what?
To only recognize peptides presented on MCH class II molecules
Where does CD8 bind to and what does it restrict?
Binds to nonpolymorphic region of MHC class 1 and restricts killing to ONLY cells presenting MHC class I
The TCR complex consists of Ag receptor, AB dimer and CD3 whihch is a signaling complex composed of which polypeptides?
Gamma, sigma, epsilon and zeta chains
antigen presenting cell-dendritic cell function?
Naive T cell activation (CD40-CD40L)
antigen presenting cell- macrophage cell function?
Effector T cell response- activation (CD40-CD40L)
APC B cell function?
Effector T cell response, B cell activation and Ab production (CD40-CD40L)
Microbial Ags enter through skin/GI/respiratory where DCs capture and take to LN. Ags that enter the blood stream are capture by…?
APCs in the spleen
What are the main differences between tissue resident DCs and activated DCs in regard to function, Expression of receptors, expression of molecules involved in T cell activation and life of Class II MHC?
Residents are to capture antigens, high express receptors (Fc/mannose), low B& ICAM-1 and IL12, short life of class II mHC Active DCs present ag to T cell, no expression of receptors, high expression of B7, ICAM1 IL12, long half like and surface molecules
IFN-gamma stimulates class II MHC expression on APCs and enhance the activation of CD4T cells. What does IFN-G and type I interferons effect?
Express class I MHC and activate CD8 T cells.
Human MHC is also call the HLA which stands for?
Human leukocyte antigen
Class I and II of polymorphic MHC genes encode human leukocyte AG (HLA) that can bind peptides and are critical to Ag presentation. Only polymorphic chain forms a binding groove for peptides to be recognized by T cells… What do class I genes (HLA-A-B-C) encode?
They encode one polymorphic heavy chain which combines with invariant B2-microglobulin, expressed on all nucleated cells
What do class II genes (HLA-D) encode, which contribute to the formation of peptide-binding groove?
They encode HLA-DP,DR,DQ which are composed of two dissimilar polymorphic chains, alpha and beta
What length of peptides and class I and class II MHCs bind?
8-10 and 10-20 respectively
The alpha chain, is glycosylated, and B2-microglobulin chains are bound how in mhc class I?
covalently
In MHC class II, the polymorphic alpha and beta chains are both glycosylated and bound non-covalently. What would be the name of the structure?
HLA-DR1
Listed are some main features of properties of MHCs, list the significance for each? 1. Co-dominant expression
2. Polymorphic genes (many different allels are present)
3. Class II express on DCs,Mø, B cells
Class I express on all nucleated cells
- Increase # of MHC molecules that can present Ags to T cells
- Different people can respond to different Ags
- CD4 helper T cells interact
- CD8 CTL can kill virus infected cell
Peptides that bind MHC class I molecules are viruses and intracellular microbes that infected the host cell while peptides that bind to class I MHC are recognize by?
CD8 cytotoxic T lymphocytes
Class II MHC recognize APCs that present extracellular pathogens and Ags to activate?
CD4 T helper cells
An anchor residue on the peptides bind to residues in the class I and II grooves, holding it in place, and vary for different MHC alleles. A single MHC can bind….
Many different peptides which have the same anchor residue
Polymorphic residues of class I and II MHC molecules are located?
in the peptide-binding clefts and the alpha helixes around the clefts
The cleft is where peptides lie in the peptide bind clefts. MHC class I clefts are closed while class II are open, this results in?
class II molecules accomodate longer peptides than class I molecules
Why do alpha/beta T cells only recognize linear peptides?
Because only peptides bind to MHC molecules and conformation is lost during enzymatic processing of Ags into peptides
Why do A/B T cells recognize cell-associated and not soluble Ags?
MHC stably bound peptides stably and complexes are located on the cell surface
Why do CD4 T cell recognize extracellular and CD8 T cells receognize intracellular Ags?
CD4 because MHC II display peptides that are taken up from extracellular environment by APCs via pinocytosis
CD8 becaue MHCI present peptides from cytosolic proteins including intracellullar pathogens
What are the 5 steps involved in the class II mHC pathway?
- Uptake of extracellular proteins / antigen
- Processing of proteins in lysosomal vessicle
- Biosynthesis/transport of class II MHC in ER to endosomes
- Processed antigens bind to groove in MHC
- Express antigen/MHCII on cell curface to bind CD4 -> T helper cell
The HLA-DM editing mechanism works to ensure the presentation of only the protein fragments most relevant for eliciting an immune response. What are it’s three major functions?
- Causes dissociation of clip from MHC II binding groove
- Stabilizes and prevents degredation of empty MHCII
- Helps bind Ag frament to open, stabilized MHCII groove
What are the 5 stesp involved in synthesis and protection of class II MHC in the pathway?
- Class II MHC synthesized in ER
- Transported with invariant chain (which blocks binding groove) to vesicle
- HLA-DM removes clip,stabilizes MHCII, facilitates Ag binding
- Transported to surface
- Expression of peptide-MHC on cell surface
What are the 5 main steps involved in class I MHC pathway?
- Proteins produced in cytosol with virus
- Proteolytic degradation of proteins
- Transport of peptides from cytosol to ER by proteasome
- Class I MHC chaperone switched with B2micro, activates antigen transporter binds Ag by ERAP, binds to Ag
- Peptide-MHC I complex brought to surface to activate CD8 and Cytotoxic T cell
When fragments of cells infected with intracellular microbes (CD8) are ingested by DCs (use CD4), what can happen?
Cross-presentation of Ags. Some DCs have both MHC 1 and 2. So the DC with bound MHCII, can pick up intracellular virus peices and present to CTL by MHC 1
Main difference between class II MHC and class I?
Class II use T helper cells which secrete cytokines to either a) activate marcphages to kill or b) help B cells make antibodies to antigens
Class I use cytotoxic T cells kills the presenting cell immediately
What are immunodominant peptides?
Peptides of a degraded antigen that are the ones that bind to the to MHC molecules to be recognized by T cells, some may respond and some may not respond to an antigen, just depending on structural constraints
B cells differentiate in response to Ags and other signals (cytokines from CD4) into Ab secreting cells. No antigen processing is needed for BCRs and anitbodies to recognize, bind and eliminate. How are the antigens expressed to to B cells?
microbial surfaces (capulsar or envelope Ags) or solube form (secreted toxins)
