1.5 T-Cell Diversity Flashcards
The T-cell is a 2 component membrane bound molecule. What are those components?
Alpha and beta chain with a variable and constant region
TCR requires additional ___ to enable signaling
Proteins
What are the types of additional proteins?
CD3 contains an Epsilon (ε) and Delta (δ)
CD3 contains and Epsilon (E) and Gamma (γ)
What 2 events occur for the formation of T-cell receptor proteins in both the alpha and beta chain?
Somatic recombination and the formation of T cell receptor genes
What regions does the alpha chain have?
Joining, variable and constant regions
What regions does the beta chain have?
Variable, diversity, joining, and constant regions
Recognition of antigen by T cell requires the ___
MHC molecule
- T cells DON’T bind free antigens
CD8 binds the ___ domain of ___
alpha 3
MHC class I
CD4 binds the ___ domain of ___
Beta 2
MHC class II
What must interact with a MHC molecule for T cell stimulation?
TCR and co-receptor
CD4 T cell coreceptors are
D1, D2, D3, and D4
CD8 T cell coreceptors are
alpha and beta
Describe CD8 T cell interaction with a virally infected cell
- Antigen present on surface of MHC class I
- T cell recognizes the antigen because of MHC I and the coreceptor on the T cell
- T cell is stimulated for apoptosies
Describe CD4 T cell interaction with a macrophage
- Antigen presented on surface of MHC class II
- T cell with coreceptor recognizes it and it stimulates the production of cytokines that act on the macrophage to activate it and kill
- Cytokines are released from macrophage and go into blood to attract more phagocytes
Describe CD4 T cell interaction of B cell
- Antigen presented on surface of MHC II on B cell
- T cell releases cytokines that stimulates the B cell to turn into plasma cell
- Plasma cell secretes antibodies
What’s the region called that binds the peptide?
Peptide binding groove
MHC antigens are small ___ peptides
Linear
Describe the linear peptides presented by MHC I
- They’re 8-10 amino acids long
- Both ends are firmly attached to MHC I molecule
Describe the linear peptides presented by MHC II
- 12-15 amino acids long
- Both ends are floppy
Steps for extracellular antigen binding to MHC class II
- Extracellular antigen is taken in by endocytotic vesicle
- Phagolysosome chews up the antigen and peptides form
- MHC is released from ER and golgi and binds to antigen
- MHC class II presents peptide at cell surface
What is the invariant chain?
A peptide that’s stuck onto the antigen binding region on the MHC class II and prevents molecules from binding to the antigen binding region
Steps for removing a invariant chain
- Invariant chain blocks antigen binding region on MHC class II in ER
- Placed into vesicle and goes to cytosol
- Invariant chain is cleaved and CLIP fragment’s left
- HLA-DM releases CLIP and allows MHC II to bind antigens
Peptides produced in the cytosol are transported to the ___ in virally infected cells
ER
Steps for transporting peptides from viruses into the ER
- Proteosome chews up the proteins from virus
- Peptide fragments form
- TAP (transporter associated w/ antigen processing) transports the peptides from cytosol to ER
MHC class I is stabilized by ___ until ___ binds. Why does it do this?
Calnexin
beta2-microglobulin
Keeps MHC I inactive and prevents it from binding things
Steps for intracellular pathogen binding to MHC class I
- Calnexin stabilizes MHC I until beta2-macroglobulin binds
- beta2-macroglobulin binds to MHC I and calnexin leaves
- beta2-macroglobulin forms the peptide loading complex with calreticulin, tapasin, TAP, ERp57, and PDI
- TAP brings in a peptide and it binds to MHC I making it mature MHC I
- MHC class I dissociates from peptide loading complex and leaves ER
What happens if the peptide is too long for MHC class I?
ERAP removes N-terminal AA to give peptide 8-10 AA
Tissue specificity for MHC Class II
Antigen presenting cells and thymic epithelium
- B cells, macrophages, and dendrites
Tissue specificity for MHC Class I
T cells, B cells, macrophages, dendritic cells, and neutrophils
What is MHC called in humans?
Human Leucocyte Antigens
Human MHC Class I isotypes and what is their morphology?
HLA-A (highly polymorphic)
HLA-B (highly polymorphic)
HLA-C (highly polymorphic)
HLA-E (oligomorphic)
HLA-F (monomorphic)
HLA-G (oligomorphic)
Human MHC Class II isotypes and what is their morphology?
HLA-DM (oligomorphic)
HLA-DO (Oligo and monomorphic)
HLA-DP (polymorphic)
HLA-DQ (polymorphic)
HLA-DR (highly polymorphic and oligomorphic)
What is the possible number of alleles for homozygotes?
3 Class I genes and 3 Class II genes
What is the possible number of alleles for heterozygotes?
6 Class I genes and 16 Class II genes
Describe intrallelic conversion
1 allele from maternal and 1 from paternal –> highly homologous genes allow for crossing over and now you have new allotype
Describe gene conversion
DNA fragment loops around and you get a new cross section
- Gene conversion from the same chromosome
All variability in MHC is located where?
peptide binding groove
T/F: TCR must recognize the MHC marker and the antigen in context with the MHC marker
True
What are the 2 classes of T-cell receptors?
alpha:beta T cell
γ(gamma):δ(delta) T cell
γ(gamma):δ(delta) T cell
- In the gut epithelium tissue
- At a lower concentration
- Don’t display MHC restriction
- 5% of T cells
- Respond quickly
Steps for transposase activity:
- Transposase cleaves a gene encoding a receptor of innate immunity
- Inserted transposon splits receptor gene into 2 segments
- Chromosomal rearrangements move transposase genes to different chromosome
