Lecture 7: MHC and Antigen Presentation to T Cells

Question 1

Cell mediated immunity is due to

Answer 1

The direct action of T cells

Question 2

T cells also HELP with

Answer 2

HELP mount a robust Ab-mediated humoral immune response directed against extracellular pathogens

Question 3

TCR

Answer 3

T cell antigen receptor
Glycoprotein
Only recognizes peptides bound to MHC molecules

Question 4

Each T cell recognizes

Answer 4

Only one specific foreign peptide

Question 5

CD4+ T helper cells recognize

Answer 5

Peptide Ags in the context of MHC class II molecules that are expressed by DCs, macrophages and B cells

Question 6

CD8+ cytotoxic T cells recognize

Answer 6

Peptides associated with MHC class I molecules

Question 7

Differential requirement for CD4 and CD8 in the context of MHCs relates to

Answer 7

The fact that CD4 and CD* attach to the non-variable part of the MHC class II and I molecules, respectively

Question 8

Does recognition of the peptide Ag by the TCR activate T cells?

Answer 8

No, this is not sufficient. There must also be co-stimulatory molecules expressed by APCs

Question 9

T-cell activation leads to production of

Answer 9

IL-2, which controls clonal expansion of the specific T cells

Question 10

Th1

Answer 10

Helper T cell
Activated Th1 produce IFN-y which activate macrophages and help development of cytotoxic T cells to kill virus infected cells
(intracellular microbes)

Question 11

Th2

Answer 11

Helper T cell
Help B cells develop into memory cells and plasma cells that produce antibodies
Produce IL-4, important for B cell proliferation
(extracellular microbes)

Question 12

a/b T cells vs yd T cells

Answer 12

ab T cells are conventional T cells
yd T cells have some characteristics of ab T cells but have broader specificity for unconventional Ags such as HSP and phospholipids

Question 13

TCR associates with what

Answer 13

CD3, a signaling complex

Question 14

MHC class II expressed on

Answer 14

Only on professional Antigen Presenting Cells APCs

DCs, macrophages, B cells

Question 15

MHC class I expressed on

Answer 15

All nucleated cells in the body

Question 16

Two classes of MHC genes encode

Answer 16

Human leukocyte antigen HLA that can bind peptides and are thus critical to Ag presentation

Question 17

Polymorphic regions of MHC class I and II

Answer 17

Peptide binding domains
MHC I- binds peptides 8-10 AAs long
MHC II- binds peptides 10-20 AAs long

Question 18

Class I molecules composed of

Answer 18

Polymorphic a-chain, non-covalently attached to the non-polymorphic B2-microglobulin
alpha-chain is glycosylated

Question 19

Class II molecules composed of

Answer 19

Polymorphic a-chain non-covalently attached to polymorphic B chain
Both chains are glycosylated

Question 20

Anchor residue

Answer 20

Residues on peptides that bind to residues in class I and II grooves and vary for different MHC alleles

Question 21

Co-dominant expression of MHC

Answer 21

Both parental alleles of each MHC gene are expressed, increasing number of different MHC molecules that can present peptides to T cells

Question 22

Polymorphic genes and MHC

Answer 22

Ensures that different individuals are able to present and respond to different microbial peptides

Question 23

Peptides that bind to MHC class I are derived from

Answer 23

Viruses and other intracellular microbes that have infected host cells
(endogenous pathway)

Question 24

Peptides binding to MHC class II are derived from

Answer 24

Mostly Ags and extracellular pathogens taken from the environment

Question 25

Dendritic cell class II expression

Answer 25

Constitutive, increases with maturation | Increased by IFN-y

Question 26

Dendritic cell principal function

Answer 26

Initiation of T cell responses to protein antigens

Question 27

Macrophage Class II expression

Answer 27

Low or negative, inducible by IFN-y

Question 28

Macrophage principal function

Answer 28

Effector phase of cell-mediated immune responses

Question 29

B lymphocytes class II expression

Answer 29

Constitutive, increased by IL-4

Question 30

B lymphocyte principal function

Answer 30

Ag presentation to CD4+ helper T cells in humoral immune response

Question 31

CD40 and CD40L

Answer 31

CD40 is a costimulatory protein found on professional APCs and is required for their activation. The binding of CD40L on T cells to CD40 activates the APC

Question 32

Microbial Ags entering through skin, GI and respiratory tracts are responded to by

Answer 32

Dendritic cells and transported to lymph nodes

Question 33

Ags entering the blood stream are captured by

Answer 33

APCs in the spleen

Question 34

Tissue resident DC expression Vs activated DC expression

Answer 34

Tissue resident DCs express mannose and Fc receptors | Activated DCs express molecules involved in T cell activation (B7, ICAM-1, IL-12)

Question 35

NK cells and T cells produce

Answer 35

``` IFN-y, which stimulates class II MHC expression on APCs and thus enhances the activation of CD4+ T cells (IFN-y and type I interferons have similar effect on expression of MHC class I molecules and activation of CD8+ T cells) ```

Question 36

a/b T cells recognize

Answer 36

Linear peptides | Cell-associated, non-soluble Ags

Question 37

CD4+ T cells recognize

Answer 37

Extracellular Ags because MHC II molecules display peptides that are taken up from the extracellular environment of APCs by pino/phagocytosis

Question 38

CD8+ T cells recognize

Answer 38

Intracellular Ags because MHC I molecules present peptides from cytosolic proteins including intracellular pathogens

Question 39

CLIP

Answer 39

``` Class II associated invariant chain peptide -There are a lot of self peptides in the ER which are prevented from binding to class II MHC by the invariant chain ```

Question 40

HLA-DM

Answer 40

Causes dissociation of CLIP from peptide binding groove of MHC II Stabilizes and prevents degradation of the empty MHC II Facilitates the binding of Ag fragments to the open, stabilized binding groove

Question 41

TAP

Answer 41

Transporter associated with Ag processing | Transports processed cytosolic peptides into the ER to be matched with MHC I molecule

Question 42

How do DCs present Ags for CD8+ T cells

Answer 42

``` Fragments of cells infected with intracellular microbes are ingested by DCs Ags are transported into cytosol and presented in association with class I MHC molecules to CD8 T cells Thus, DCs are able to present extracellular Ags by the class I pathway ```

Question 43

Immunodominant peptides

Answer 43

Processing generates multiple different peptides | Immunodominant peptide is the best fit