(Section B: Immunology) Lecture 14: T-Cell Immunity I Flashcards
What components are T-Cell Receptors made up of?
- Variable region (V)
- Constant region (C)
- Transmembrane region
- Cytoplasmic tail
What protein subunits for the TCR?
Alpha and Beta
What does the V-region in TCRs contain?
The antigen binding site
True or False:
TCRs don’t directly recognize antigens
True
What do TCRs recognize?
Mostly recognize peptides (from proteins) presented by MHC molecules
Epitope
Part of antigen actually recognized
What is the epitope for TCRs?
Peptides
How are peptides presented to TCRs?
- Antigen broken down into peptide fragments
- Carried by MHC to TCRs
Give examples of:
Peptides interacting with MHC
Inside the cell:
1. Self proteins
2. Virus infections
Outside the cell:
1. Bacterial infections
2. Parasitic infections
3. Self proteins
What are the classes of MHC?
- Class II MHC
- Class I MHC
Class II MHC
- Recognized by TH cells (CD4+)
- Made up of two protein chains (alpha and beta)
Class I MHC
- Recognized by TC Cells (CD8+)
- Made up of one protein chain (alpha)
What is the MHC presenting peptide fragments known as?
Antigen Presentation
MHC Restriction
T cells can only recognize antigens presented by MHC
Why is a large diversity of MHC molecules necessary?
Increases the range of peptides that can be recognized by T Cells
What advantage does MHC diversity impart?
Evolutionary survival advantage against infectious disease
Describe the structure of the peptide binding groove in both classes of MHCs
- Beta sheets on the floor of the groove
- Alpha helices on the walls of the groove
How does the composition of peptide-binding groove differ between MHC Class II and MHC Class I?
MHC Class II:
* Alpha and Beta domains form peptide-binding groove
MHC Class I:
* Alpha and Alpha domains form peptide-binding groove
What size of peptides can the classes of MHC proteins present to T Cells?
Class I proteins:
* “Closed” peptide-binding groove
* Binds peptides of 8-10 amino acids
Class II proteins:
* “Open” peptide-binding groove
* Binds peptides of 13-24 amino acids
Where are the classes of MHC proteins expressed?
MHC Class I
* Inside the cell
* Expressed by all nucleated cells (not in RBCs)
MHC Class II
* Outside the cell
* Expressed by specialized cells (“Antigen presenting cells”, all have phagocytic ability)
* E.x. B Cells, Macrophage, Dendritic cells, Epithelial Thymic Cells
What types of Antigen-presenting cell types are there?
- Professional
- Nonprofessional
What are examples of professional Antigen-Presenting Cells?
- Dendritic cells
- Macrophages
- B cells
What are examples of nonprofessional Antigen-presenting cell types?
- Fibroblasts (skin)
- Glial cells (brain)
- Pancreatic beta cells
- Thymic epithelial cells
- Intraepithelial lymphocytes
- Vascular endothelial cells
Professional Antigen-Presenting cells
Express Class II MHC molecules at high levels
* Delivers activating signals to T cells
Nonprofessional Antigen-presenting cells (APCs)
Can express Class II MHC and coostimulatory molecules when stimulated by infection
What role do thymic epithelial cells play?
Play a role in clonal selection during T cell development
How do peptide antigens get to Class I MHCs?
- Protein gets degraded by proteosome
- Peptide fragments go through TAP into ER
- MHC I carries peptide through Golgi to outside the cell
How do peptide antigens get to Class II MHCs?
- Antigen gets carried into cell via Vesicle and receptors
- MHC Class II goes from ER to Golgi and to cytoplasm
- Peptides are broken down from early to late endosome, receptors are recycled
- MHC Class II and peptide endosomes are merged together
- MHC Class II leaves cell
What is unique about Dendritic Cells?
They can initiate both CD4 and CD8 T Cell Activation by Cross-Presentation of Antigen
Allorecognition
Recognition of “other” (non-self)
Direct vs. Indirect allorecognition
Direct:
* T cell recognition of donor (nonself) MHC presenting donor (nonself) or recipient (self) peptides
Indirect:
* T cell recognition of recipient (self) MHC presenting donor (nonself) peptide (allopeptide)
What disease exploit the MHC Class II Pathway?
- Flesh eating disease
- Toxic shock syndrome
Diseases caused by Bacterial Infections
What is inflammation caused by in diseases that exploit the MHC Class II Pathway?
Superantigen proteins (SEA, SEB etc.)
What does the superantigen protein do?
Essentially prevents the MHC protein and the T cell from separating (causing overexpression)