Lecture 6 Adaptive Immunity - Antigen Presentation Flashcards
How are mature naive T cells activated?
antigen presentation by APC
- TCR recognizes self MHC /antigen combination
- APC is usually a DC that uses either MHC I (CD8) or II (CD4)
What is significant about professional APCs?
can present with either MHC I or MHC II
What does MHC stand for? What is another name for it?
Major Histocompatibility Complex = transplant compatibility
-also known as Human Leukocyte Antigen (HLA) = WBC function
What kind of cells can express MHC I or MHC II molecules?
MHC I
- alpha chain+B2 microglobulin
- can be expressed by all nucleated cells
- erythrocytes not nucleated
MHC II
- alpha chain+beta chain
- professional APCs are DCs, Macrophages, B cells and can also express MHC I
What are MHC/HLA loci?
encode different versions of alpha and beta chains to make different peptide binding sites
-creates variability in MHC presentation
How are genes inherited from each parent?
As halotypes from each parent
- the alleles are co-dominant and expressed equally
- only results in slight variations in MHC antigen binding sites
How do T cells tell whether an antigen presented is endogenous or exogenous?
MHC is used to present peptide antigens to T Cells
Peptides are loaded on 1 of 2 different classes of MHC based on ORIGIN of antigen
Endogenous Antigens
- synthesized inside cell during viral infection
- loaded onto MHC I
Exogenous Antigens
- englufed by phagocytic cells and loaded onto MHC II
- virus can be exogenous too if phagocytosed outside of cell
What are the steps of the endogenous pathway?
- Tag abnormal intracellular proteins in cytosol with Ubiquitin
- Tagged proteins are shuttles to enzyme complex called proteasome which shreds protein into peptides
- Peptides are transported by TAP into RER lumen for MHC I loading
- RER proteins ERp57, calnexin, tapasin, calreticulin stabilize MHC I complex (alpha chain+B2 microglobulin) for loading
- ERAP processes peptides to optimal size for peptide-binding groove of MHC I
- Peptide loaded on MHC I and complex transported to cell membrane for presentation
What are the steps of the exogenous pathway?
- Extracellular antigens (eg. bacterial antigens) are phagocytosed/endocytosed
- no ubiquitin and antigen always in vessicle - Digestion in phagosome/endosome creates peptides
- Vessicles containing peptides fuse to vessicles from golgi apparatus containing MHC II
- The MHC II in golgi vessicle stabilized by invariant chain which blocks binding site from peptides
- Invariant chain digested by pH drop and formed into CLIP which is exchanged for peptides to bind MHC II
- MHC II/peptide complex transported cell membrane
Explain
What are the APCs with MHC II?
Thymic Epithelial Cells
-positive and negative selection of immature T Cells
DCs and Macrophages (professional APCs)
-activate and mature naive CD4 T cells
B Cells (professional APCs)
-become activated by TH Cells
What are the APCs with MHC I?
Thymic Epithelial Cells
-positive and negative selection of immature T Cells
DCs and Macrophages (professional APCs)
- activate and mature naive CD8 T cells
- can use Cross Presentation
All Nucleated Cells
-target cells for cytotoxic response
