Antigen presentation by MHC class II Flashcards
MHC class II present peptides to:
CD4+ molecules
Main roles of MHC class II antigen presentation
T helper cells
Production of cytokines
Main 4 subsets of Th cells
Th1 -> produce IL-2, INF-gamma
Th2 -> produce IL-4, IL-5
Th17 -> produce IL-17
Tregs -> produce TGF-beta, IL-10
Function of Th1 response
enhances cellular immunity
Function of Th2 response
enhances humoral response
MHC class II/peptide complexes recognised by CD4+ T cells
CD4 molecule on helper t cell recognises class II heavy chain
T cell receptor recognises MHC class II
Key points of MHC class II antigen processing pathway
Source of antigen
Capture of antigen
Proteolysis (degradation) of antigen
Role of accessory proteins
Antigen presenting cells
macropinocytosis
almost like drinking up cellular fluid; captures smaller particles than phagocytosis
Endocytic route of antigen capture
receptor-mediated endocytosis
phagocytosis
macropinocytosis
Peptide generation in endocytic vesicles
Controlled breakdown of antigen into peptides
Antigen moves through acidic endosomal compartments -> initiates protein unfolding
Enzyme that catalyses disulphide bond at low pH in protein unfolding for class II processing
GILT-IFNg inducible lysosomal reductase
Lysosomal and endosome proteases (there are 4)
Cathepsins
Endopeptidases
Exopeptidases
Asparaginyl endopeptidase (AEP)
MHC class II antigen presentation can be blocked by:
Chloroquine/NH4Cl - prevents acidification
Protease inhibitors
CLIP
Class II associated invariant peptide
Invariant chain (Ii) function
In the ER the MHC class II molecule is complexed with a polypeptide called the invariant chain. This prevents peptides from binding and it chaperones class II to endosomal/lysosomal compartments
Invariant chain degradation
Degraded into fragments by proteases - one of these fragments is CLIP, which binds in the MHC class II peptide groove
What are professional antigen presenting cells (APCs)?
Heterogenous population of leukocytes
Specialised to have class II MHC molecules
Three main examples of professional APCs
Dendritic cells
Macrophages
B cells
Dendritic cells
Immature in peripheral organs; migration to the follicles of secondary lymphoid organs becoming matures
MHC and other co-stimulatory molecules on surface
Key role: activate naive t cell responses
Conventional DCs
Capture pathogens
V efficient at achieving t cell response
Plasmacytoid DCs
primarily monitor for viral infections and produce cytokines
Interactions of APCs with T cells
More than just the TCR and MHC complex
First contact (adhesion)
MHC/TCR interaction
Co-stimulation (activation or inhibition)
Activation - release of cytokines/granzyme/perforin
Immunological synapse
between t cell and target cell; secretory domain