Linking: TCR, MHC and Co-receptors

Question 1

What does tcr recognize

Answer 1

Peptide mhc (pmhc) completes on surgface of apc - on self mhc

Question 2

What does tcr recognition require

Answer 2

T cell apc contact and leads to formation of immunological synapse - strong and long

Question 3

What is in tcr complex

Answer 3

Includes many things =
2 zeta chains, itams, tcr flanked by cd3

Question 4

What does itam stand for

Answer 4

Immunoreceptor tyrosine based activation motif

Question 5

What happens when tcr binds

Answer 5

Intraclelualr signalling triggered - allows T cell to be activated

Question 6

Describe tcr recognition subunit = gen

Answer 6

Heterodimer - alpha beta
Trans membrane - not secreted
Stay on surface of T cells

Question 7

What are the mature T cell types based on

Answer 7

2 types of mature T cells based on components of heterodimer =
Alpha beta tcr = majority
Gamma delta tcr = <10%, recognize diff Ligands/develop diff

Question 8

Define clonotypic

Answer 8

T cell makes clones
Cells of a given clone all have identical receptors - all clones have same receptors

Question 9

Name the 2 regions of tcr

Answer 9

Variable region = binds mhc, specific to antigen
Constant region = closer to cell membrane

Question 10

What happens in individual lymphocytes

Answer 10

Adaptive immune receptor genes undergo rearrangement in individual lymphocytes

Question 11

How many adaptive immune cell repcetros

Answer 11

Billions of bcrs and tcrs

Question 12

How many innate immune receptors

Answer 12

100 or less= why its less specific

Question 13

What do bcr and tcr genes undergo

Answer 13

DNA rearrangement

Question 14

Name gene segments

Answer 14

Variable = v
Diversity = d
Joining = j
Constant = c

Question 15

What are gene segments

Answer 15

Short dna sequences at T cell receptor loci that encode diff regions of variable domain of receptor

Question 16

Describe alpha chain

Answer 16

V j and c domains

Question 17

Describe beta chain

Answer 17

V d j and c domains (can choose from 2 constant domains)

Question 18

What makes up one tcr - rearrangement

Answer 18

Take on fo each and make alpha and beta and then group those together = make up tcr

Question 19

Where does tcr rearrangement occur

Answer 19

Thymus

Question 20

Define somatic recombination

Answer 20

Recombination of gene segments in T cell receptor genetic loci to produce a functional gene

Question 21

Explain somatic recombination

Answer 21

Germaine dna —> recombination —> rearranged dna —> transcription, splicing, translation
= happens for alpha and beta
Then stick them together

Question 22

Describe tcr interaction

Answer 22

Tcr recognizes peptide in context of mhc
Does not recognize peptide alone
Has to interact with peptide and mhc - not just peptide alone

Question 23

Name the 2 types of apcs

Answer 23

Professional
Non professional

Question 24

Which cells are professional apcs

Answer 24

Dcs
Macrophages
Activated B cells

Question 25

What do professional apcs express

Answer 25

Express mhc class 1 and 2 molecules Express costimulatory molecules when activated

Question 26

Name non professional apcs

Answer 26

All nucleated cells in body

Question 27

what do non professional apcs express

Answer 27

Express mhc class 1 molecules under normal conditions Do not express costimulatory moelcules

Question 28

Why 2 type of MHC

Answer 28

To cover the 2 main types of pathogens = intracellular vs extra cellular pathogens

Question 29

Describe MHC class 1 Moelcules

Answer 29

Bind and present peptides generated within the cell = endogenous peptides, including self proteins

Question 30

Describe MHC class 2 Moelcules

Answer 30

Bind and present peptides of extra cellular origin = exogenous peptides

Question 31

What does Mhc class 1 activate

Answer 31

Cd8+ T cells = become cytotoxic T cells

Question 32

What does Mhc class 2 activate

Answer 32

Cd4+ T cells - become helper T cells

Question 33

Describe mhc class 1 molecule - specific parts

Answer 33

Alpha= trans membrane, has 3 domains B2 microglobulin = non trans membrane and constant, binds noncovalently = hydrophobic interact

Question 34

Describe mhc class 2 molecule - specific parts

Answer 34

Alpha and beta chain trans mem Each has 2 domains

Question 35

What does mhc class 1 require to be expressed stably

Answer 35

Peptide Mhc class 1 alpha chain B3 microglobulin

Question 36

What does mhc class 2 require to be expressed stably

Answer 36

Peptide Mhc class 2 alpha Mhc class 2 be chains

Question 37

What does each chain of mhc have

Answer 37

Several immunoglobulin like domains

Question 38

What are ig like domains

Answer 38

Modular secondary structure shared among many molecules of immune system = adhesion molecules, tcr

Question 39

What do ig like domains consist of

Answer 39

~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

Question 40

Describe peptide binding groove of mhc molecule

Answer 40

Antigen peptide binding cleft or groove facing out

Question 41

Describe what faces cell membrane of mhc

Answer 41

More conserved area faces cell memrbane

Question 42

What do mhc have- differences

Answer 42

Allele specific differences in their primary sequence - these differences located mostly around in peptide binding cleft

Question 43

What does peptide binding groove of both mhcs have

Answer 43

Alpha helices and beta sheets

Question 44

Describe peptide binding groove mhc class 1

Answer 44

Mhc class 1 molecules bind shorter peptides = 8-10aa Closed off= more limited in size of peptide that can bind

Question 45

Describe peptide binding groove mhc class 2

Answer 45

Length of peptides = no constrained but is at least 13 aa

Question 46

Describe structure of pMHC-tcr interaction

Answer 46

Mhc at bottom Peptide in it Tcr on top with key domains in various colours

Question 47

Why are co receptors needed

Answer 47

Tcr-pmhc interaction = low affinity Co receptors needed so can stay attached for all 3 signals

Question 48

Name co receptors and what they do

Answer 48

Cd4 and cd8 Physically interact with mhc molecules constant regions = stabilizes, allowing long interaction

Question 49

Describe cd4

Answer 49

Single chain tm protein 4 ig like domains

Question 50

Describe cd8

Answer 50

Heterodimer Linked by disulfide bond Each chain has one ig like domain Both chains = tm proteins

Question 51

Describe the 2 functions of cd4 and cd8 co receptors

Answer 51

Bind mhc molecule and enhance affinity of tcr-pmhc interaction Initiation of signalling from tcr (signal 1) - co receptors v important for intracellular signalling