TCRs Flashcards
What is the primary function of TCs?
- To monitor the INTRACELLULAR environment of the host cell
- Exist to help the body evade/deal w/ pathogens
What are CD4+ and CD8+ T cells functions?
cd8-target virus infected cell
cd4- function in two types of immunity
1. interacting w/ MO leading to activation–>activation of cytokines
2. help BCs (in form of cytokines) to `differentiate into PC–>production of speciaized Abs
Ways TCR similar to BCR
- contains 1 Ag binding site (2 in Abs)
- contain variable and constant regions
Ways TCR different to BCR
- Where expressed
- Ag that is recognized
- Affinity of Ab for Ag much higher
TCR biochemical characterizations
- disulfide linked dimer
- both chain glycoproteins
- transmem protein ONLY (no sluable form, unlike Ig)
- constant and variable region
How is CD3 involved in TCR?
TCR alpha/beta chains need help of CD3 molecule to make it to surface
CD3
2 pairs of them (4 total) form the TCR complex which escorts TCR A/B chain to surface of cell and is responsible for SIGNAL TRANSDUCTION (ST)
-Cytoplasmic tails of TCR to short to tranduce signal
Once Ag bound to TCR there is ST by CD3 to cell–>Activates cell
Organization/Rearrangement of TCR genes
Organized similar to Ig molecule
- Alpha –>V and J
- Beta –> V, D, and J
Generating diverse repertoire of TCR
- recombination of diff gene segments
- recombination of diff # of gene segments
- Imprecise joining of gene segments
- P and N addition
- Assembly of diff combination of rearranged TCR chains
What differs TCR in way it generates diversity?
Unlike Ig genes, SOMATIC HYPERMUTATION does not occur - (no increase in affinity for Ag)
Which has greater diversity TCR or BCR?
TCR
-Alpha has no D regions (like in Ig light chain) BUT has many J regions that contribute to its high diversity
Why is this high diversity important?
So TCR can recognize peptide from any Ag it might encounter (since does not undergo somatic hypermutation)
How do BCR and TCR recognize Ag?
BCR - recognize structure (naive Ag)
TCR - recognize short peptide fragments presented by MHC molecules
How does affinity for Ag compare?
TCR - have weak affinity for peptide/MHC
MHC job?
Present Ag
MHC class 1
- alpha chain non-covalently attached to beta 2 microglobulin (stabilizes alpha chain)
- alpha 3 more constant
- alpha 1 and 2 form groove for variable part of MHC C1
- ->w/in groove are residues required to contact peptide
MHC class 2
- have alpha and beta chain
- most polymorphism in beta 1 domain (alpha 1 monomorphic)
- grooved formed by beta 1 and alpha 1
- ->groove contains specific residues for peptide contact
Can single MHC molecule bind multiple peptides?
Yes, if they share certain sequences
How does MHC restrict presentation of Ag on T-cells?
TCR can ONLY recognize AG when presented as peptide from MHC molecule
Process of restriction presentation
- APC presents peptide to TCR and CD3 sends signal to activate cell
- If have same Ag, but presented on FOREIGN MHC- TCR wont recognize MHC and no activation
- Self MHC w/ diff Ag being presented - no activation
Alloreactivity
Strong TC response to foreign MHC (caused by transplant rejection)
Expression of MHC 1
Expressed by ALL nucleated cells
Expression of
MHC 2
Expressed on a SUBSET of hematopoietic cells that are APC and thymic stromal cells
Function od CD4 and CD8 om TCs?
Function as co-receptors
–increasing alpha/beta TCR sensitivity for peptide MHC
Where do CD4/8 cells interact on MHC?
On NON-VARIABLE REGIONS
- MHC 1–> CD8 on CD8+ TCs will react w/ more constant region (alpha 3)
- MHC C2–> CD$ on CD4+ TCs will interact with non-polymorphic beta 2
How do some TCRs recognize presented Ag differently?
Some do NOT require Ag to be presented (gamma/delta)
- can see MHC by itself
- or bind directly to native Ag
MHC haplotype
Complete set of alleles found w/in an animals MHC
Where do MHC alleles come from?
One from each parent
-expressed co-dominantly
How does increase diversity between MHC haplotypes help?
More divergent haplotypes will present more peptides from any pathogen than more related haplotypes
MHC diversity caused by? (2)
- Polymorphism due to allele variation
- Polygeny due to the fact that there are several diff MHC genes w/ similar functions
Why is MHC diversity important to survival of HIV?
More polymorphism - longer time from serocenversion to live
Relative Risk of specific MHC type
Look for expression of particular MHC allele w/ and w/o in individuals w/ disease and compare it to those individuals w / and w/o allele
- no association when = 1
- > 1 = allele associated w/ disease
Where do peptides presented by MHC 1 come from?
From cytosolic pathogens or self-proteins in cytosol
-present to CD8+ T-cell–>kill presenting cell
Where do peptides presented by MHC 2 come from?
Peptides derived from intravesicular pathogens or extracellular pathogens that are taken in
-present to CD4+ T-cells–>kill pathogen or activate B-cells
How does MHC class 1 process Ag?
Newly syn proteins in CYTOSOL Ub and fragemented into peptides by PROTEOSOME
- peptides associated with TAP and move to mem of ER and then to lumen
- peptide placed in binding groove of MHC C1
- peptide complex goes to cell surface
How does MHC class 2 process Ag?
Ag ingested and fragmented by PROTEASES
- peptides move into endosomal compartments and are placed in binding groove on MHC C2
- displace CLIP (usually in groove to prevent` self-binding of peptides) and goes to surface
Cross-presentation of Ags?
MHC C1 can express exogenous Ags (where it usually present cytosolic)
MHC C2 can present cellular Ags (where it usually presents extracellular ones)
What are SUPERAGs?
Act as bridge btween TCR and MHC and stimulate TCs
-DO NOT NEED REC OF PEPTIDE
Comparison of SuperAg and Conventional Ag
- Higher freq of responsive T-cells (SA)
- SA are not MHC restricted
- SA does not require processing
- SA does not bind to peptide groove of MHC
Ex of superAg?
TSST-1 –> Causes toxic shock syndrome since by allowing TCR to bind to MHC
- causes overproduction of cytokines
- complications occur
- death
