MHC

Question 1

What are cogenic strains of MHC?

Answer 1

strains in which the endogenous MHC is replaced by an entire MHC locus form another strain

Question 2

What are recombinant strains of MHC?

Answer 2

strains in which only a portion of the endogenous MHC complex has been relplaced by MHC of another haplotype (breeding from 1 strain into another)

Question 3

Which cells express MHC I?

Answer 3

all cells in body (except RBCs)

Question 4

Which cells express MHC II?

Answer 4

APCs (antigen presenting cells): activated T cells, B cells, macrophages, dendritic (other APC), thymic epithelium

NB: neurons do NOT express Class II but brain microglia (of monocyte/macrophage lineage) do express class II

Question 5

How do T cells recognize viral antigens in virus infected cells?

Answer 5

only as complex with MHC antigens

[For both Cytotoxic T cells and T helper cells: the ability of T cells to recognize a particular MHC as self depends on the MHC haplotype(s) present in the thymus in which they matured]

Question 6

Which T cells express CD4?

Answer 6

Helper T

Question 7

Which T cells express CD8?

Answer 7

Cytotoxic T

Question 8

Which T cell marker is on all T cells?

Answer 8

CD3?

Question 9

Which MHC class interacts with CD4?

Answer 9

II

Question 10

Which MHC class interacts with CD8?

Answer 10

I

Question 11

Single mutations in T cells alter MHC . Which mutation (in B6 mice) alters Class I? Class II?

Answer 11

bm1: Class I
bm12: Class II

Question 12

Name the MHC class that presnet antigens that originate within the cell. (like viruses and tumor antigens)

Answer 12

MHC Class I

Question 13

Name the MHC class that present antigens that originate outside the cell.

Answer 13

MHC Class II

Question 14

Can antigens be presented on both class I and class II MHC?

Answer 14

yes: “cross” pathways
eg: a virus that ends up in endosomes

Result: leads to two different types of immune rxns

Question 15

How are most bacteria handled?

Answer 15

Most are extracellular:
T cell help –> Ab production –> processed for Class II presentation

TH cells recognize exogenous antigen which is phagocytosed and presented by Class II

Question 16

How are most viruses handled?

Answer 16

Most are inside cell: require CTL (cytotoxic T cell) to kill infected cell

CTL recognize antigen synthesized inside cell, which is presented by class I

Question 17

Steps of Class I MHC Presentation

Answer 17

1) Proteosome cleaves antigens into fragments
2) TAP system transports them to lumen of RER
3) Newly made fragments bind to newly-made Class I MHC and get shipped in vesicle to fuse with PM
4) CTL receptor binds Class I MHC + antigen fragment

Question 18

Steps of Class II MHC Presentation

Answer 18

1) Antigen phagocytosed by APC
2) Proteolytic cleavage within endosome
3) Binding to Class II MHC in endosome
4) export of antigen/MHC complexes to PM
5) TH receptor binds to Class II MHC + antigen fragment

Question 19

Answer for Class I molecules:

• peptide binding domain?
• nature of peptide-binding cleft? (open/closed)
• size of peptides (# of AAs)
• anchor residue motifs (where on peptide?)
• nature of bound peptide?

Answer 19

• peptide binding domain? alpha 1/alpha2
• nature of peptide-binding cleft? closed at both ends
• size of peptides: 8-10 AAs
• anchor residue motifs: STRONG motifs; anchors at both ends of peptide; generally hydrophobic
• nature of bound peptide? extended structure with both ends interacting with MHC cleft but middle arches up away from MHC

Question 20

Answer for Class II molecules:

• peptide binding domain?
• nature of peptide-binding cleft? (open/closed)
• size of peptides (# of AAs)
• anchor residue motifs (where on peptide?)
• nature of bound peptide?

Answer 20

• peptide binding domain? alpha 1/BETA1
• nature of peptide-binding cleft? OPEN at both ends
• size of peptides: 13-18 AAs
• anchor residue motifs: WEAK motifs; anchors residues distributed along the length of the peptide
• nature of bound peptide? extended structure that is held at constant elevation above MHC

Question 21

What is the fate of an antigen-presenting cell with no B7?

Answer 21

anergy of TH cell

Question 22

What are the two types of CD4+ cells (T helper)

Answer 22

Th1 (inflammatory);

Th2 (helper)

Question 23

What is the function of Th1 cells?

Answer 23

(inflammatory)

B-cell proliferation; 
polyclonal Ig secretion; 
*cytotoxcity; 
*suppression of Ig secretion;
*delayed-type hypersenstivity (DTH)

Note: * means unique to this cell

Question 24

What is the function of Th2cells?

Answer 24

(Helper)

B-cell proliferation;
polyclonal Ig secretion;
*HELP FOR SPECIFIC Ab!

Note: * means unique to this cell

Question 25

What cytokines are released from Th1 cells?

Answer 25

(pro-inflammatory) ``` IL-2,* IL-3; GM-CSF; *IFN-gamma, *TNF-Beta TNF-alpha ``` Note: * means unique to this cell

Question 26

What cytokines are released from Th2 cells?

Answer 26

IL-3; *IL- 4, 5, 6, 10; GM-CSF; TNF-alpha

Question 27

Which cytokines are released from any/all CD4+ cells?

Answer 27

IL3, GM-CSF; TNF-alpha

Question 28

What is the role of the thymus for T cells?

Answer 28

maturation and selection

Question 29

What is negative selection of T cells?

Answer 29

Round II of selection: T cells that recognize self-antigens are not allowed to exit the thymus and are eleminated Removes Tcells that show dangerously high reactivity to self

Question 30

What is positive selection of T cells?

Answer 30

Round I of selection: ONLY cells with TCR that match self with MHC (with at least some affinity) are allowed to mature Purpose: weed T cells with TCRs that don't match a self-MHC (bc it is useless)

Question 31

What is "round III" of selection? (immune response creation)

Answer 31

takes place after T cells mature: Match self MHC + foreign peptide well? Y: survive and divide --> create immune response N: die the set of foreign antigens encountered determines which immature T cells will make immune responses, proliferate, and give rise to long-lived descendants

Question 32

Which class of MHC activates the immune system?

Answer 32

MHC II

Question 33

Which class of MHC responds to virally infected cells?

Answer 33

MHC I

Question 34

What is TAPASIN?

Answer 34

protein that fxns as bridge btwn TAP and MHC-I in the presentation pathway (MHC-I) -edits the peptide repertoire, making sure only high affinity peptides are presented

Question 35

What is ERAP?

Answer 35

MHC-I presentation pathway ER aminopeptidase: trims peptides in ER prior to binding to MHC class I. Creates peptides that are the correct size

Question 36

What is the "invariant chain" in the MHC-II pathway?

Answer 36

binds to MHC-II in ER and facilitates transport from ER to endosomes; portion of chain is bond in class II peptide groove

Question 37

What is DM's role in the MHC-II pathway?

Answer 37

edits peptide repertoire, making sure only high affinity peptides are presented

Question 38

What do Myeloid dendritic cells (mDC): - produce? - express?

Answer 38

- produce: IL-12 - express: TLR 2, 4 effective in antigen presentation

Question 39

What do plasmacytoid dendritic cells (mDC): | -express?

Answer 39

express: TLR 7, 9; high levels of IFN-alpha (impt in viral infections) lymphoid origin?

Question 40

How are antigens captured?

Answer 40

- passing epithelium of skin, GI tract, resp tract - lymph node collects antigen from epithelium and CT - blood borne antigens are captured by APCs in spleen

Question 41

What (receptors/molecules) do immature dendritic cells produce?

Answer 41

purpose: antigen capture Express Fc receptors and mannose receptors (help them capture things) - low expression of T cell activating molecules (B7; ICAM-1; IL-12) - short half-life of MHC-II molecules

Question 42

What (receptors/molecules) do mature dendritic cells produce?

Answer 42

(Purpose: antigen presentation to T cells) -high expression of molecules involved in Tcell activation (B7, ICAM-1, IL-12) - no expression of Fc receptors or mannose receptors - longer half life (>100hr) - 7x amt of surface molecules compared to immature DCs

Question 43

What is responsible for immature to mature DC conversion?

Answer 43

TLR ligation (when DC eat pathogen and receives TLR ligation

Question 44

What MHCs do APCs express?

Answer 44

Class I and Class II

Question 45

How do DCs present antigens, and what's the response?

Answer 45

*NATIVE T CELL ACTIVATION Present with costimulator (B7) to CD28 of native T cell to activate the Native T cell toward differentiation to effector T cells and clonal expansion

Question 46

How do macrophages present antigens, and what's the response?

Answer 46

EFFECTOR T CELL ACTIVATION (AND activation of macrophages: cell-mediated immunity) Macrophage presents antigen to Effector T cell which then results in killed microbe

Question 47

How do B cells present antigens, and what's the response?

Answer 47

EFFECTOR T CELL ACTIVATION (AND B cell activation and Ab production --> humoral immunity) B cells present antigen to effector T cells --> Abs

Question 48

What process allows for viral peptides to be bound to MHC I molecules?

Answer 48

DCs can ingest viral infected cells and display peptides bound to MHC I --> cross presentation provides way for naive CD8 T cells to get activated

Question 49

What type of peptides are on the majority of class I and class II?

Answer 49

self-peptides (but no reaction bc tolerance has been established; unless autoimmunity)

Question 50

Where are most of the genes for MHC I and II?

Answer 50

MHC is POLYGENIC (and polymorphic) --> variation HLA Genetic Region: Class I: A, B, C Class II: DP, DQ, DR Note: genes for invariant chain and Beta2m are on other chromosomes

Question 51

Where do most of the polymorphisms lie in MHC?

Answer 51

in peptide binding groove