12 – linking innate and adaptive:TCR, MHC & co-receptors Flashcards
TCR recognizes peptide-MHC (pMHC) complexes on
surface of APC
recognition leads to
formation of an immunological synapse
Recognition requires
T cell:APC contact
TCR complex includes
TCR, CD3, z(zeta) chain, ITAMs
what is ITAM
immunoreceptor tyrosine-based activation motif
…signaling is triggered
Intracellular
TCR recognition subunit
Heterodimer of chains
Transmembrane proteins
Not secreted
2 main types on mature T cells based on components of heterodimer
αβ TCR
𝛾𝛿 TCR (<10%)
Clonotypic
cells of given clone all have identical receptors
what are Variable (V) & constant (C) regions
V – specificity to antigen
C – closer to membrane
BCR & TCR genes undergo … for…
DNA rearrangement
Specificity & diversity
TCR rearrangement happen in
thymus
Gene segment
Variable –V
Diversity – D
Joining – J segments
Constant – C genes
α chain:
V, J, C domains
β chain:
V, D, J, C domains
Group α chain +β chain =
T cell
Somatic recombination/gene rearrangement
Recombination of gene segments in TCR genetic loci to produce functional gene
Types of APCs
Professional APC
Non-professional APC
Professional APC : example, expresses…
DCs, macrophages, activated B cells
-Express MHC class I & class II molecules
-Express costimulatory molecules when activated
Non-professional APC: example, expresses…
All nucleated cells in the body
NK cells
-Express MHC class I molecules only, under normal conditions
-Do not express costimulatory molecules
ΜHC class I molecules bind & present?
Bind & present peptides generated within the cell – endogenous peptides
Included self proteins
MHC class II molecules bind & present?
Bind & present peptides of extracellular origin – exogenous peptides
ΜHC class I molecules activate
CD8+ T cells – cytotoxic function
MHC class II molecules activate
CD4+ T cells – helper function once differentiated
ΜHC class I molecules structure
α chain (transmembrane) + β2 microglobulin (non-transmembrane & invariant (constant), binds noncovalently – hydrophobic interaction)
α chain has 3 domains
MHC class II molecules structure
α chain + β chain (both transmembrane)
Each have 2 domains
ΜHC class I molecules Require 3 components to be expressed stably:
Peptide – have to be bound inside cell before expressed
MHC class I α chain
β2 microglobulin
MHC class II molecules Require 3 components to be expressed stably:
Peptide
MHC class II α
MHC class II β chains
Each chain of MHC has several
Ig-like domains (immunoglobulin)
-Modular secondary structure shared among molecules of immune system
Adhesion molecules
TCR
-Consist of domain oF ~100 aa, α helices, β strands
Stabilized by intrachain disulfide bonds
Ag peptide-binding cleft groove facing IN/OUT?
OUT
…facing cell membrane
More conserved area
MHC have allele specific differences in primary sequence
Differences located around peptide-binding cleft
Peptide binding groove of both MHC-I & II have α helices, β sheets
MHC class I molecules - size of peptides
Bind short peptides of 8-10 aa
MHC Class II molecules - size of peptides
Bind peptides at least 13 aa long
Structure of pMHC-TCR interaction
MHC at bottom
Peptide in middle
TCR on top with key domains
TCR-pMHC interaction … affinity
low affinity interaction
needed – allow/stabilizes interaction
co-receptors
examples of co receptors, what do they do
CD4&CD8 co-receptors physically interact with MHC molecules
Constant regions
CD4
Single chain transmembrane protein
4 Ig-like domains
CD8
Heterodimer
Linked by disulfide bond
Each chain has 1 Ig-like domain
Both chains are transmembrane proteins
Functions of CD4 & CD8 co-receptors (2)
1.Bind MHC molecule & enhance affinity of TCR-pMHC interaction
2.Initiation signaling from TCR (signal 1)
