Antigen Presentation & Processing - Diebel Flashcards
What is anergy?
The TCR recognizes a MHC and binds
but there is NO CD80/86 being expressed on the APC
-T cell will get destroyed/deleted
What does CTLA-4 do on the T cell surface?
~24 hours after T cell activation it will express CTLA-4
CTLA-4 competes with CD28 for binding to CD80/86
It has a higher affinity for CD80/86
Blocks stimulatory effect you get from CD80/86 and is important to prevent overstiumlation
Dendritic cells
What do they do?
How do they express their receptors and costimulatory molecules
- Most effective APC
- Present peptides, viral antigens, and allergens
- Immature in peripheral tissues = low expression of MHC II (so always expressing it)
- Mature in lymphoid tissues = high expression of MHC II
- Constitutively express B7 (CD80/86) and other co-stimulatory molecules
How do DCs take up antigen?
What T cells do they activate?
-uptake antigen by endocytosis and phagocytosis
-activate naive T cells, effector T cells, memory T cells.
When do macrophages express MHC II and their co-stimulatory molecules?
What do they present to T cells?
- They must be activated by phagocytosis and cytokines to express these
- Present particulate antigens to T cells
When do B cells express MHC II and co-stimulatory molecules?
What do they present to T cells?
-Constitutively express MHC II (increases w/ activation)
-must be activated by antigen binding to antibody to express co stimulatory molecules
-Present soluble antigens, toxins, and viruses
Cyctosolic Pathway?
What MHC molecule goes with this?
- Endogenous pathway
- Antigen is inside of cell and gets broken down by proteasome
- Antigen peptides secreted into RER
- Bind to class MHC I molecules
- MHC II loaded with peptide goes to golgi to get brought to the surface for presentation
Endocytic Pathway:
- MHC II is in RER and binding site is occluded
- exogenous antigen is uptaken by endocytosis
- As MHC is travelling from golgi to surface, it fuses with vesicle with antigen peptides
- Presents antigen peptides on surface of cell
Cytosolic Proteolytic System:
- During normal growth cycle you have constitutive proteosome
- Inflammation –> Type 1 IFN produced –> switching of beta subunits (immunoproteasome) –> activity changes –>proteins are cut into different lengths to fit into MHC I molecule groove.
What is the function of TAP1/TAP2?
What size peptide does it like?
- Transporter associated with antigen processing
- Peptide bind to transporter protein heterodimer complex –> TAP1 and TAP2
- Tap1/Tap2 extends across membrane of RER and transports peptides into lumen of the RER
- Tap has affinity for peptides 8-16 amino acids long
Function of ERAAP?
- MHC I is picky and likes peptides to be 9 amino acids long
- ERAAP trims the peptide to this length
What kind of peptides does MHC I like to present?
-its on all cells except RBCs remeber.
-
Defective ribosomal products (DRiPs) - sometimes we just don’t make proteins correctly so we have to fess up, display these mistakes, and get killed
- defective proteins = defective DNA
-
Viral proteins- Virus infected cells have 20S proteasome (induced by IFN gamma and TNF alpha)
- degrades and presents viral proteins
- T cells recognize these proteins and kill infected cells
What chromosome are the instructions for MHC I molecule on?
Most everything is on chromosome 6 (Tap, HLA-A, B, C,
HLA-DQ, DP, DR)
Beta2 microblogulin is on chromosome 15
What is the normal ratio of CD4:CD8 T cells?
2:1
~65% CD4
~35%CD8
How is low MHC I related to low overall T cell #’s, specifically less CD8+ T cells?
In thymus, T cells start as double positive for CD4 and CD8
If you only display 1% of normal MHC I molecules you will mostly select for CD4 b/c most cells will come into contact with MHC II molecules
—-> Less CD8 cells
