L13 - Antigen recognition by T cells Flashcards
Define the 2 types of T cell receptors.
1) 95% = conventional T cells with α and β chains
2) 5% = nonconventional T cells: with δ and γ chains
Compare the genetic variability and Ag specificity between conventional and unconventional TCRs.
Conventional = Vα, Vβ domains contain 3 hypervariable / complementarity determining regions (CDRs) to determine Ag binding specificity
Unconventional = much lower CDR variability, recognize restricted sets of antigens
List the 3 mechanisms for generating TCR diversity?
1) Somatic gene recombination:
i) VDJ gene segments for β chain
ii) VJ gene segments for α chain
2) Junctional diversity: TdT adds N or P nucleotides
3) β chain often uses 3 reading frames in D gene segment **
Which has more diversity: BCR or TCR?
TCR
List some differences in diversity generation processes of TCR and BCR **
TCR:
- No somatic hypermutation (cannot increase Ag binding affinity after made)
- No switch recombination (TCR sequence fixed in mature T cells)
- No secreted form (only on T cell surface)
List some similarities in diversity generation processes of TCR vs BCR?
Both undergo:
- Somatic recombination of DNA
- Junctional diversity
- Transcriptional activation
Can T cell responses be transferred from one person to another like antibodies?
No
T cells are MHC restricted: Only able to recognize Ag presented by self MHC
Describe the T cell receptor complex and its parts.
- TCR α/β chains = antigen receptor
- CD3: signaling complex = transduce intracellular signals upon antigen binding (function like ITAM in BCR)
- CD4 (monomer) or CD8 (dimer): co-receptor
Describe the binding complex between a T cell and an APC?
- TCR complex with CD3 for intracellular signalling/ co-receptor
- TCR binds to peptide antigen presented by MHC-I or II on the APC
- TCR- Ag binding is helped by either CD4 or CD8 co-receptor
Define the 2 types of T cells with distinct MHC preference?
- CD8+ T cells bind α3 domain of MHC class I from all nucleated cells
- CD4+ T cells bind β2 domain of MHC class II from APCs
Compare the MHC class I and II in their structure?
- For MHC class I = α subunit and β2-microglobulin (invariable,never changes) (α1 +α2 +α3 +β2, 8 - 10 amino acids)
- For MHC class II = α subunit and β subunit (α1 + α2 +β1 +β2, 12-30 amino acids)
Define MHC restriction?
T cell is restricted to recognize a peptide antigen bound to self MHC molecules only
List the processes that generate MHC diversity?
- Polygeny: both class I and class II has multiple gene loci
- HLA alleles are co-dominantly expressed
- High HLA diversity with diverse polymorphism within the population
Describe the genetic variation in the loci for MHC-I?
MHC-I = α subunit and β2-microglobulin
- β2-microglobulin = not polymorphic
- 3 polymorphic genes for α chain: HLA-A, HLA-B, HLA-C **
- 3 other genes for non-classical MHC-I: HLA-E, HLA-F, HLA-G (not for conventional T cells, not for peptide presentation)
Describe the genetic variation in the loci for MHC-II?
MHC class II = α subunit and β subunit
Multiple genes for both chains:
- HLA-DP, HLA-DQ, HLA-DR ** for peptide antigen presentation
- HLA-DM, HLA-DO = intracellular proteins for loading MHC-II
Which chromosome is vital for the genetic variation in MHC?
short arm of chromosome 6
Explain how the HLA alleles coding for MHC are expressed?
HLA alleles are co-dominantly expressed
i.e. an individual can express 6 different types of functional MHC-I and 6-8 different types of MHC-II (DRB has multiple genes)
Which HLA alleles coding for MHC are highly polymorphic?
HLA class 1: A,B,C genes
HLA Class 2: DRB gene
Explain how peptide specificity is achieved in MHC?
Each MHC allele can bind and present distinct sets of peptides
MHC polymorphism*** affects peptide specificity
» determines which peptide antigens are recognized in different individuals
MHC-I and II are always present on cell surfaces and await the loading of peptide antigens. T or F?
False
“Empty” MHC molecules are extremely unstable
in normal cells, MHC are bounded with self-peptides
Compare the type of peptide antigen presentation pathways between MHC-I and MHC-II? Which antigens are presented?
MHC-I = Cytosolic pathway: present endogenous antigens: intracellular bacteria, virus, self-proteins, proteins in cytosol
MHC-II = Endocytic pathway: present Exogenous antigens: extracellular microbes, protein
Describe the process of peptide antigen presentation via MHC-I?
- Endogenous antigens in cytosol cleaved by proteasomes** into peptide antigens
- MHC-I made in the ER, stabilized with Chaperone Protein**
- TAP** (transporter associated with antigen processing) transports peptides into ER: select peptide with right length** to load into MHC-I, Release Chaperone
- Golgi body translocates MHC-I/peptide complexes to cell surface» present to CD8+ T cells
Which cells carry MHC-I? How is it used to alert the immune system of infections?
All nucleated cells (not RBC)
- MHC/self-peptide = not degraded
- MHC/peptide from pathogen = targeted destruction
Describe the process of endocytic pathway via MHC-II ?
- Antigen endocytosis»_space; enclosed in vesicle»_space; combine with lyzosomes to degrade protein
- MHC-II made and folded in ER, stabilized with chaperone protein»_space; transport via vesicles from Golgi
- MHC-II vesicles fuse with endolyzosomes»_space; Peptide fragments loaded»_space; MHC-peptide complex translocated to cell surface
> > Present to CD4+ T cells
