Antigen uptake, processing, and presentation Flashcards
What is self -MHC restriction?
the fact that T cells can only respond to antigen that is presented on self MHC
Antigen recognition by CD4+ cells is class __ restricted?
Class II MHC
Antigen recognition by CD8+ cells is class __ restricted?
Class I MHC restricted -the target cell and the CTL must share the same allelic form of class I MHC molecules.
Professional APCs (macrophages, B cells and dendritic cells) express..?
class II MHC molecules and costimulatory molecules
Nonprofessional APCs such as skin fibroblasts and endothelial cells can be induced to express class II MHC molecules and/or costimulatory molecules by?
IFN-γ
How do antigen presenting cells deliver costimulatory signals?
via B7 family members like CD80 and CD86
Dendritic cells constitutively express class___MHC and ___molecules.
Class II MHC and B7 molecules
B cells constitutively express class II MHC but only express B7 following….
activation
What antigen presenting cell only expresses class II MHC and B7 upon activation?
Macrophages
Name 6 non-professional antigen presenting cells
- Fibroblasts (skin)
- Glial cells (brain)
- Pancreatic beta cells
- Thymic epithelial cells
- Thyroid epithelial cells
- Vascular endothelial cells
Prof. APCs: Antigen uptake
Dendritic cell: endocytosis and phagocytosis
Macrophage: Phagocytosis
B cell: receptor-mediated endocytosis
Prof. APCs: Activation
DC: PRRs and PAMPS
Macrophage: PRRs and T cell help enhances it
B cell: antigen recognition
Prof. APCs: MHC class II expressivity
DC: increases with activation (can express low levels constitutively)
Macrophage: Increases with activation
B cell: increases with activation (can express low levels constitutively)
Prof. APCs: Costimulatory activation
DC/Macrophage/B cell: up-regulation of CD80/86 with activation
Prof. APCs: T cell activation
DCs: Naive, effector, memory (widest range)
Macrophage/B cells: effector and memory
Dendritic cells: location when resting and activated
Resting: in circulation and peripheral tissues
Activated: T cell zones (SLOs) and tertiary tissues
Macrophages: location when resting and activated
Resting: circulation and peripheral tissues
Activated: SLOs in the subcapsular cortex of lymph nodes and the marginal zones of the spleen as well as peripheral tissues
B cells: location when resting and activated
Resting: circulation and SLOs (follicles)
Activated: SLOs of the B/T cell interface, germinal centres, and marginal zones
What is the role of IL-2?
Activating T cells and causing them to replicate and divide into effector and memory T cells
How is IL-2 produced?
T cell receives signals 1 and 2 from the APC
Signals T cell to produce IL-2 and the IL-2 receptor
The IL-2 then acts back on the T cell itself
What is the target cell for CD8+ T cells ?
Almost all nucleated cells -because they express abundant class I MHC (except neurons)
Cytosolic Pathway processes:
endogenous (intracellular) antigens and presents them on the cell surface in association with class I MHC molecules.
Endocytic pathway processes:
exogenous (extracellular) antigens and presents them on the cell membrane in association with class II MHC molecules.
general Steps in the cytosolic pathway
- Endogenous antigens targeted by ubiquination
- Antigens degraded by the proteasome
- Peptides can either undergo further degradation by exopeptidases into amino acids OR be taken into the TAP and then to the RER
- Then they are presented via class I MHC
What is the TAP?
Transporter of Antigenic Peptides
What is the function of the TAP? What peptides does it have a high affinity for?
Has a high affinity for peptides that are 8-13 aa in length
Carries cytosolic peptides across the RER
What is the role of calnexin the cytosolic pathway?
promotes folding and inhibits premature α chain degradation
What is the role of calreticulin the cytosolic pathway?
Calreticulin is a molecular chaperone that promotes proper folding
What is the role of tapasin?
Tapasin brings TAP close to the class I MHC molecule, allowing the class I MHC molecule to acquire the antigenic peptide.
What is the role of the ERp57 complex
associates with the calreticulin/class I MHC/tapasin complex to stabilize the complex and allow the class I MHC molecule to be released once antigenic peptide is acquired
6 Steps of the cytosolic pathways occurring in the rough ER
- newly synthesized α chains of class I MHC associate with the molecular chaperone calnexin
- β2-microglobulin binds to the α chain, calnexin is released and the class I MHC molecule associates with calreticulin and tapasin.
- Tapasin brings TAP close to the class I MHC molecule, allowing it to acquire the antigenic peptide.
- ERp57 associates with the calreticulin/class I MHC/tapasin complex to stabilize the complex
- Class I MHC released once peptide is acquired
- peptide-MHC class I complexes are then transported in vesicles from the RER through the Gogli complex to the plasma membrane.
What is responsible for receptor-mediated endocytosis for B cells?
Membrane bound immunoglobulin
During the endocytic pathway, what happens to the antigen once it is ingested?
degraded into peptides by hydrolytic enzymes within the acidic environment of the endocytic compartment
Where do the class II MHC molecules originate from in the endocytic pathway?
Polysomes within the RER
Explain the process of class II MHC preparation and antigen binding starting at the RER for the endocytic pathway (6 steps)
- Class II MHC alpha and beta chains bind the invariant chain in the RER
- MHC complex is routed through the Golgi to the endocytic pathway compartments
- Invariant chain is degraded, leaving the CLIP fragment behind
- Exogenous antigen is taken up, degraded and routed to endocytic pathway compartments
- HLA-DM mediates exchange of CLIP for the antigenic peptide
- Class II MHC-peptide is transported to the plasma membrane
What is the role of the invariant chain?
To prevent binding of endogenous antigen to the class II MHC
What is the role pf HLA-DO and HLA-DM in the endocytic pathway?
HLA-DM catalyses the exchange of CLIP for the antigenic peptide
HLA-DO modulates HLA-DM
*both are non-classical class II MHC molecules
What is the difference between class I and class II MHC with respect to binding antigenic peptides within the RER?
Class I MHC molecules bind antigenic peptides within the RER while class II molecules do not because the invariant chain occupies the peptide- binding cleft
What is the purpose of having 2 segregated systems?
the segregation of the pathways means that the immune system will be optimally responsive to either an intracellular or extracellular infection
- cytosolic pathway: dispatch T cells
- endocytic pathway: antibody
What is cross presentation and which cells can do it?
Dendritic cells are able to present exogenous antigen to cytotoxic T lymphocytes in the context of class I MHC molecules
What is the point of cross-presentation?
professional antigen-presenting cells that are not infected by virus are still able to activate cytotoxic T lymphocytes.
How does DC licensing occur?
DCs present antigen to CD4+ T cells
CD4+ T cells then become activated if they recognize the antigen
License DCs to present exogenous antigens via class I MHC
How are exogenous nonpeptide antigens expressed? (like lipids and glycolipids)
via CD1
- resembles class I MHC
- associates with the ß-microglobulin
Which cells express CD1?
professional and non-professional APCs
Which 2 cytokines can induce the expression of CD1?
GM-CSF and IL-3
how many known subsets of CD1 are there?
4
What types of cells recognize CD1 and through what receptor?
A wide range of T cell types, including NKT cells and T cells that express a γδ T cell receptor
