Linking: TCR, MHC and Co-receptors Flashcards
What does tcr recognize
Peptide mhc (pmhc) completes on surgface of apc - on self mhc
What does tcr recognition require
T cell apc contact and leads to formation of immunological synapse - strong and long
What is in tcr complex
Includes many things =
2 zeta chains, itams, tcr flanked by cd3
What does itam stand for
Immunoreceptor tyrosine based activation motif
What happens when tcr binds
Intraclelualr signalling triggered - allows T cell to be activated
Describe tcr recognition subunit = gen
Heterodimer - alpha beta
Trans membrane - not secreted
Stay on surface of T cells
What are the mature T cell types based on
2 types of mature T cells based on components of heterodimer =
Alpha beta tcr = majority
Gamma delta tcr = <10%, recognize diff Ligands/develop diff
Define clonotypic
T cell makes clones
Cells of a given clone all have identical receptors - all clones have same receptors
Name the 2 regions of tcr
Variable region = binds mhc, specific to antigen
Constant region = closer to cell membrane
What happens in individual lymphocytes
Adaptive immune receptor genes undergo rearrangement in individual lymphocytes
How many adaptive immune cell repcetros
Billions of bcrs and tcrs
How many innate immune receptors
100 or less= why its less specific
What do bcr and tcr genes undergo
DNA rearrangement
Name gene segments
Variable = v
Diversity = d
Joining = j
Constant = c
What are gene segments
Short dna sequences at T cell receptor loci that encode diff regions of variable domain of receptor
Describe alpha chain
V j and c domains
Describe beta chain
V d j and c domains (can choose from 2 constant domains)
What makes up one tcr - rearrangement
Take on fo each and make alpha and beta and then group those together = make up tcr
Where does tcr rearrangement occur
Thymus
Define somatic recombination
Recombination of gene segments in T cell receptor genetic loci to produce a functional gene
Explain somatic recombination
Germaine dna —> recombination —> rearranged dna —> transcription, splicing, translation
= happens for alpha and beta
Then stick them together
Describe tcr interaction
Tcr recognizes peptide in context of mhc
Does not recognize peptide alone
Has to interact with peptide and mhc - not just peptide alone
Name the 2 types of apcs
Professional
Non professional
Which cells are professional apcs
Dcs
Macrophages
Activated B cells
What do professional apcs express
Express mhc class 1 and 2 molecules
Express costimulatory molecules when activated
Name non professional apcs
All nucleated cells in body
what do non professional apcs express
Express mhc class 1 molecules under normal conditions
Do not express costimulatory moelcules
Why 2 type of MHC
To cover the 2 main types of pathogens = intracellular vs extra cellular pathogens
Describe MHC class 1 Moelcules
Bind and present peptides generated within the cell = endogenous peptides, including self proteins
Describe MHC class 2 Moelcules
Bind and present peptides of extra cellular origin = exogenous peptides
What does Mhc class 1 activate
Cd8+ T cells = become cytotoxic T cells
What does Mhc class 2 activate
Cd4+ T cells - become helper T cells
Describe mhc class 1 molecule - specific parts
Alpha= trans membrane, has 3 domains
B2 microglobulin = non trans membrane and constant, binds noncovalently = hydrophobic interact
Describe mhc class 2 molecule - specific parts
Alpha and beta chain trans mem
Each has 2 domains
What does mhc class 1 require to be expressed stably
Peptide
Mhc class 1 alpha chain
B3 microglobulin
What does mhc class 2 require to be expressed stably
Peptide
Mhc class 2 alpha
Mhc class 2 be chains
What does each chain of mhc have
Several immunoglobulin like domains
What are ig like domains
Modular secondary structure shared among many molecules of immune system = adhesion molecules, tcr
What do ig like domains consist of
~100 aa, alpha helices, beta sheets
Stabilized by intrachain disulfide bonds
Cleft made up of alpha helices and other domains
B sheets hold peptide at bottom
Alpha helices make up peptide binding cleft
Describe peptide binding groove of mhc molecule
Antigen peptide binding cleft or groove facing out
Describe what faces cell membrane of mhc
More conserved area faces cell memrbane
What do mhc have- differences
Allele specific differences in their primary sequence - these differences located mostly around in peptide binding cleft
What does peptide binding groove of both mhcs have
Alpha helices and beta sheets
Describe peptide binding groove mhc class 1
Mhc class 1 molecules bind shorter peptides = 8-10aa
Closed off= more limited in size of peptide that can bind
Describe peptide binding groove mhc class 2
Length of peptides = no constrained but is at least 13 aa
Describe structure of pMHC-tcr interaction
Mhc at bottom
Peptide in it
Tcr on top with key domains in various colours
Why are co receptors needed
Tcr-pmhc interaction = low affinity
Co receptors needed so can stay attached for all 3 signals
Name co receptors and what they do
Cd4 and cd8
Physically interact with mhc molecules constant regions = stabilizes, allowing long interaction
Describe cd4
Single chain tm protein
4 ig like domains
Describe cd8
Heterodimer
Linked by disulfide bond
Each chain has one ig like domain
Both chains = tm proteins
Describe the 2 functions of cd4 and cd8 co receptors
Bind mhc molecule and enhance affinity of tcr-pmhc interaction
Initiation of signalling from tcr (signal 1) - co receptors v important for intracellular signalling
