12 – linking innate and adaptive:TCR, MHC & co-receptors

Question 1

TCR recognizes peptide-MHC (pMHC) complexes on

Answer 1

surface of APC

Question 2

recognition leads to

Answer 2

formation of an immunological synapse

Question 3

Recognition requires

Answer 3

T cell:APC contact

Question 4

TCR complex includes

Answer 4

TCR, CD3, z(zeta) chain, ITAMs

Question 5

what is ITAM

Answer 5

immunoreceptor tyrosine-based activation motif

Question 6

…signaling is triggered

Answer 6

Intracellular

Question 7

TCR recognition subunit

Answer 7

Heterodimer of chains
Transmembrane proteins
Not secreted

Question 8

2 main types on mature T cells based on components of heterodimer

Answer 8

αβ TCR
𝛾𝛿 TCR (<10%)

Question 9

Clonotypic

Answer 9

cells of given clone all have identical receptors

Question 10

what are Variable (V) & constant (C) regions

Answer 10

V – specificity to antigen
C – closer to membrane

Question 11

BCR & TCR genes undergo … for…

Answer 11

DNA rearrangement
Specificity & diversity

Question 12

TCR rearrangement happen in

Answer 12

thymus

Question 13

Gene segment

Answer 13

Variable –V
Diversity – D
Joining – J segments
Constant – C genes

Question 14

α chain:

Answer 14

V, J, C domains

Question 15

β chain:

Answer 15

V, D, J, C domains

Question 16

Group α chain +β chain =

Answer 16

T cell

Question 17

Somatic recombination/gene rearrangement

Answer 17

Recombination of gene segments in TCR genetic loci to produce functional gene

Question 18

Types of APCs

Answer 18

Professional APC
Non-professional APC

Question 19

Professional APC : example, expresses…

Answer 19

DCs, macrophages, activated B cells
-Express MHC class I & class II molecules
-Express costimulatory molecules when activated

Question 20

Non-professional APC: example, expresses…

Answer 20

All nucleated cells in the body
NK cells

-Express MHC class I molecules only, under normal conditions
-Do not express costimulatory molecules

Question 21

ΜHC class I molecules bind & present?

Answer 21

Bind & present peptides generated within the cell – endogenous peptides
Included self proteins

Question 22

MHC class II molecules bind & present?

Answer 22

Bind & present peptides of extracellular origin – exogenous peptides

Question 23

ΜHC class I molecules activate

Answer 23

CD8+ T cells – cytotoxic function

Question 24

MHC class II molecules activate

Answer 24

CD4+ T cells – helper function once differentiated

Question 25

ΜHC class I molecules structure

Answer 25

α chain (transmembrane) + β2 microglobulin (non-transmembrane & invariant (constant), binds noncovalently – hydrophobic interaction) α chain has 3 domains

Question 26

MHC class II molecules structure

Answer 26

α chain + β chain (both transmembrane) Each have 2 domains

Question 27

ΜHC class I molecules Require 3 components to be expressed stably:

Answer 27

Peptide – have to be bound inside cell before expressed MHC class I α chain β2 microglobulin

Question 28

MHC class II molecules Require 3 components to be expressed stably:

Answer 28

Peptide MHC class II α MHC class II β chains

Question 29

Each chain of MHC has several

Answer 29

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

Question 30

Ag peptide-binding cleft groove facing IN/OUT?

Answer 30

OUT

Question 31

...facing cell membrane

Answer 31

More conserved area

Question 32

MHC have allele specific differences in primary sequence

Answer 32

Differences located around peptide-binding cleft Peptide binding groove of both MHC-I & II have α helices, β sheets

Question 33

MHC class I molecules - size of peptides

Answer 33

Bind short peptides of 8-10 aa

Question 34

MHC Class II molecules - size of peptides

Answer 34

Bind peptides at least 13 aa long

Question 35

Structure of pMHC-TCR interaction

Answer 35

MHC at bottom Peptide in middle TCR on top with key domains

Question 36

TCR-pMHC interaction ... affinity

Answer 36

low affinity interaction

Question 37

needed – allow/stabilizes interaction

Answer 37

co-receptors

Question 38

examples of co receptors, what do they do

Answer 38

CD4&CD8 co-receptors physically interact with MHC molecules Constant regions

Question 39

CD4

Answer 39

Single chain transmembrane protein 4 Ig-like domains

Question 40

CD8

Answer 40

Heterodimer Linked by disulfide bond Each chain has 1 Ig-like domain Both chains are transmembrane proteins

Question 41

Functions of CD4 & CD8 co-receptors (2)

Answer 41

1.Bind MHC molecule & enhance affinity of TCR-pMHC interaction 2.Initiation signaling from TCR (signal 1)