Antigen Presentation and the MHC Flashcards
What differentiates B cells from other APCs?
They are not phagocytic
What are macrophages in the liver called?
Kupffer cells
What are macrophages in the brain called?
Microglial cells
What are APCs in the skin called?
Langerhans’ cells
What happens to Langerhans cells from the skin when they encounter a pathogen?
They travel through the afferent lymphatics into a draining lymph node and migrate to the paracortex where they can then present antigen to T lymphocytes
Where are follicular dendritic cells found? What is their purpose?
They are found in B lymphocyte areas of lymph nodes and spleens.
They present antigen to B lymphocytes
What are the two distinct lineages of dendritic cells?
Conventional and plasmacytoid
What are plasmacytoid dendritic cells important for?
Protection against viruses. They produce large quantities of interferon in response to viral infections.
What happens to conventional dendritic cells as they mature?
They downregulate their phagocytic functions and upregulate their antigen presentation
When is B lymphocyte antigen presentation the most important?
During a secondary antibody response
Briefly describe the antigen presentation process by class I MHC.
1) Virus infects a cell
2) Viral proteins are synthesized in the cytosol
3) Peptide fragments of viral proteins are bound by class I MHC in the ER
4) Bound peptides are transported by MHC Class I to the cell surface where they can be displayed to T-lymphocytes
Briefly describe the antigen presentation process by class II MHC.
1) Antigen is take up from the extracellular space by endocytosis (macrophage) or receptor-mediated endocytosis (B-cells)
2) Acidification of maturing endosome activates proteases to degrade antigen into peptide fragments
3) Vesicles containing peptides fuse with vesicles containing class II MHC
4) Invariant chain forms a complex with MHC class II blocking binding of peptides and misfolded proteins
5) Invariant chain is cleaved leaving CLIP in the peptide binding groove
6) HLA-DM binds to class II molecule, releasing CLPI and allowing peptides to bind.
7) Presentation at cell surface
How are viral proteins degraded so that they can be presented by class I MHC?
Host cell’s proteasome (comprised of subunits LMP2 and LMP7)
What is the role of TAP-1 and TAP-2?
TAP: Transporters Associated with Antigen Processing)- transport peptides generated in the cytosol to the endoplasmic reticulum
Name three chaperone proteins that allows newly synthesized MHC Class I (alpha and Beta2 microglobulin) to assemble in the ER?
Calnexin, Erp57 and calreticulin
What is the role of ERAAP in MHC class I assembly?
ERAAP (endoplasmic reticulum aminopeptidase associated with antigen processing)- trims the protein fragments to the right length (9 amino acids) so that they can bind to MHC Class I. Following binding, the Ag/MHC class I complex can leave the ER, travel through the golgi, and be transported to the cell surface for presentation to CD8+ cytotoxic T cells.
Peptides that bind to MHC Class II molecules are generated where?
In the acidified endocytic vesicles
Where are class II MHC molecules synthesized?
Class II are synthesized in the ER.
What is the role of the invariant chain?
The invariant chain is synthesized along with class II MHC in the ER, and blocks the binding of peptides and misfolded proteins
How is the invariant chain cleaved so that Ag can bind to class II MHC?
The invariant chain is cleaved in an acidified endosome., leaving a short peptide fragment, CLIP, still bound to class II molecules.
How is the CLIP protein eventually displaced from the binding site of class II MHC?
HLA-DM binds to the molecule releasing CLIP and allowing other peptides to bind. The MHC class II molecule can then travel to the cell surface to be displayed.
What HLA-DM?
CLIP unloader/loader
Differentiate what is the peptide binding grooves of class I and class II under normal conditions (no infection)
Class I: normal self-peptide
Class II: CLIP
Can class I and class II be in the same cell at the same time?
Yes- they are in APCs (macrophages, dendritic cells and B-cells)
Differentiate the role of Th1 vs Th2 cells
Th1: activates macrophages (increases phagocytic activity)
Th2: activates B-cells (promotes growth and differentiation)
What co-stimulatory molecule is expressed on the surface of mature dendritic cells?
B7
Activation of naive T cells by antigen requires what two signals?
1) Presentation of peptide by MHC
2) Interaction between B7 on the APC and CD28 on the membrane of the T cell
The B7 co-stimulatory molecule on APCs binds to what on the T cell?
CD28
T cells that recognize peptides expressed by MHC class II on the surface of the APC are stimulated to express what ligand? What does it bind to?
CD40 ligand.
Binds to CD40, which is normally expressed on the APC.
What does binding of CD40L to CD40 induce?
B7 expression by the APC, which can now bind to CD28 on the T cell
Do B cells secrete antibody in the absence of T cells?
No- production of antibody to most antigens requires not just B cells but also T cells.
How does T cell activation of B cells work?
B cells take up antigen, then B cells process the antigen and display them via class II MHC to T cells. This process activates B-cells to produce B7, which co-stimulates CD28 on the T cell, and activates the naive T cell.
This activation of the T cell induces expression of CD40L, which engages CD40 on the B-cell, activating the T cell to produce cytokines, and allowing the B-cell to inyo plasma cells that secrete antibody.
Differentiate the activation of T cells vs the activation of B-cells (in terms of cytokines/ligand binding)
1) T cells require 2 signals (B7 and MHC/peptide), both ligand binding interactions
2) B cells are activated by cytokines produced by activated T cells
What is the immunological synapse?
Mechanism of sustained TCR engagement- a form of specialized contact
The mature immunological synapse is defined by a specific pattern of receptor segregation with a central cluster of TCRs surrounded by a ring of adhesion molecules (like LFA-1)
T helper 1 cells are classically thought to activate macrophages to become more phagocytic. Can Th1 cells also activate B-cells to produce antibodies?
Yes, but to a lesser extent than Th2 cells.
