Antigen Processing, Presentation, and Lymphocyte Development Flashcards
MCH Restriction
T-cell receptors have specificity for a particular MHC/peptide compex
Polyspecificity of MHC receptors
Many different peptides can bind to MHC receptors, but not all peptides
Which MHC receptor can accomodate longer peptides?
MHC Class II molecules can accomodate longer peptides
MCH I peptide/complexes engage TCRs with ____ co-receptors
CD8+
MCH II peptide/complexes engage TCRs with ____ co-receptors
CD4+
Which cells express MHC I?
What is the significance of this?
- All nucleated cells express MCH I
- Can present viral peptides when infected
What are 2 important properties of MHC genes?
- Polymorphic: many different alleles present in the population
- Co-dominant expression: Both parental alleles of each MHC gene are expressed
This increases the number of microbial peptides that the MHC can present to T-cells
How do Dendritic Cells act as specialized activators of naive T-cellls?
Dentric cells:
- Process foriegn antigen
- Migrate to lymph nodes where they present the antigen to naive T-cells
- Provide addtional stimulating signals necessary for T-cell activation
What role does the spleen play with regards to blood-borne antigens?
Blood-borne antigens are captured by antigen-presenting cells in the spleed
Cytotoxic T-cells present T-Cell Receptors (TCRs) with
CD__ co-receptors which binds to MHC class ___
- CD8+ co-receptors
- MCH Class I
Helper T-cells present T-Cell Receptors (TCRs) with
CD__ co-receptors which binds to MHC class ___
- CD4+ co-receptors
- MHC Class II
MHC Class I Presentation Process
- Viral protein in the cytoplasm is cleaved by proteasomes
- Cleaved products = viral peptides
- Viral peptides are transported to the endoplasmic reticulum
- Peptides combine with MHC Class I in the ER
- MCH Class I/Peptide Complex is then transfered to the cell surface where it is expressed
MHC Class II Presentation Process
- Uptake of extracellular protein antigen via endocytosis or phagocytosis
- Endosome/Phagosome fuse with Lysosome
- Protein antigen is processed to form peptides
- MHC Class II is transported via a vesicle to the endosome/phagosome
- MHC Class II/Peptide Complex is formed and transfered to be expressed on the cell surface
Cross-Presentation
- Endosomal antigen (normally presented by MHC II) is presented by MHC I (when the endosomal antigen is viral instead of bacterial/fungal)
- Occurs as a result of certain viruses only infecting certain cell types, and the immune system (Ex. Dendritic Cells) still needs to be able to present these viral antigens even when the particular virus doesn’t infect Dendritic Cells
- Follows a similar process as normal MHC I Presentation with the only difference being that the antigen source comes from endosomes instead of the cytoplasm
Are MHC without peptide presented on the cell surface?
No because MHC without peptide are inherently unstable and undergo degredation while MHC with peptide is very stable
Which cells express MHC II?
- Dendtritic Cells
- Macrophages
- B-Lymphocytes
- Thymic Epithelium
What are the cell surface antibody associated signaling receptors?
Iga and IgB
What are the T-Cell Receptor (TCR) associated signaling receptors?
CD3
What does the T-Cell Receptor (TCR) recognize and bind to?
The MHC and peptide within the complex
What components make up the MHC Class I peptide-binding cleft?
a1 and a2
What components make up the MHC Class II peptide-binding cleft?
a1 and b1
What type of molecules do MHC bind?
Peptides only (they do not bind lipids, carbohydrates, nucleic acids, etc.)
Where do MHC I peptides originate?
Where do MHC II peptides originate?
- MHC I peptides originate from intracellular viral proteins
- With the exception of cross-presentation where the viral proteins come from endosomes
- MHC II peptides originate from extraceullar pathogens
“MHC Restricted Antigen Recognition” refers to the ability of:
T-cells to respond to a given antigenic peptide, only when this antigen is bound to a specific MHC molecule
Helper T-Cell Function
Activate macrophages to kill phagocytosed microbes
Cytotoxic T-Cell Function
Kill infected cells and eliminate reservoirs of infection
Analogy between ab T-Cell receptor and Antibody
- TCR is like the Fab fragment of an antibody
- TCR has an a/b chain; antibody has a light/heavy chain
- TCR is membrane anchored; antibody can be membrane anchored as a B-cell receptor or secreted
Antibody Structure
- 2 light chains and 2 heavy chains
- Each chain has one variable domain (V) and at lesat one constant domain (C)
- Two V domains (VL and VH) make up antigen binding site
- The Fc region determines the antibody effector function
Generation of combinatorial BCR diveristy
During B-Cell development in the bone marrow:
- Multiple different V, D, and J gene segments are selected and combined to form the gene that codes the BCR
- Genetic assembly of gene segments is mediated by the enzyme Recombinsase Activating Gene (RAG)
Additional diversity is generated by enzymes that semi-randomly add/remove nucleotides at the ends of different gene segments prior to assembly by RAG
Negative Selection
- Elimination of self reactive lymphocytes during their development
- This leads to central tolerance: the immune system does not attack self
Positive Selection of T-Cells
In order to complete development, mature naive T-cells must be able to weakly bind MHC/self-peptide complexes from thymust epithelial or dendritic cells
Negative Selection (T-Cells)
If a T-Cell binds strongly to MHC/self-peptide it undergoes apoptosis
Death By Neglect (T-Cells)
- Failure of positive selection
- If a T-Cell Receptor doesn’t bind MHC/self-peptide complexes at all (no binding), it undergoes apoptosis
How does TCR gene arrangement relate to BCR gene arrangement?
- They are very similar
- TCR diversity is also generated by combination of different V, D, and J gene segments
Double-Negative T-Cells
Early in development:
T-Cells do not express CD4+ or CD8+ co-receptors
Double-Positive T-Cells
- Later in development, T-Cells express both CD4+ and CD8+
- After CD4+ or CD8+ co-receptors weakly bind MHC II or MHC I/self-peptide complexes, they stop expressing the other type of CD co-receptor
- For example, if during development CD4+ weakly binds to MHC II, that cell will stop expressing CD8+ and become a helper T-Cell
- This ensures that after maturation T-Cells only express CD4+ or CD8+, never both
Where does the following generally occur:
- T-Cell Selection
- T-Cell Activation
- T-Cell Effector Function
- T-Cell Selection –>Thymus
- T-Cell Activation –> Lymph Nodes
- T-Cell Effector Function –> Site of Infection
