Immuno 5: MHC

Question 1

What is the Major Histocompatability Complex?

Answer 1

A large cluster of genes encoding specialized glycoproteins; many functions
Initially identified through studies of transplant rejection. Has a role in antigen presentation to T cells.

Question 2

T/F: T cells ONLY recognize peptides bound to MHC molecules.

Answer 2

True

Question 3

MHC class I molecules are homo or heterodimers?

Answer 3

Heterodimer

Question 4

What is beta-2-microglobulin?

Answer 4

A protein that is not encoded within the MHC I complex gene that encodes the rest of the heterodimer but is found as one subunit (of 4) of the MHC I complex.

Question 5

How many domains are found in the alpha chain of the MHC I complex? (3 of 4 subunits).

Answer 5

3 (alpha1, 2, 3)

Question 6

What part of the MHC I complex anchors it into the cell membrane?

Answer 6

The alpha 3 domain, has transmembrane region that anchors the chain into the cell membrane.

Question 7

What secondary structure is characteristic of the peptide binding cleft of the MHC I complex?

Answer 7

extended alpha helices of alpha 1 & 2 domains

Question 8

What differentiates the MHC class II molecule from the class I molecule?

Answer 8

1- The MHC class II molecules are heterodimers that are composed of an alpha (1,2) and a beta (1,2) chain (MHC I has 3 alpha and a beta-2-microglobulin subunit. 
2- The ends of the binding clefts of class II molecules are open (hot dog in a bun model), class I are closed.

Question 9

Are both the alpha and beta chains encoded by the MHC Class II locus?

Answer 9

Yes.

Question 10

In the MHC class II molecule, what two domains come together to form the peptide binding cleft?

Answer 10

Alpha 1 and beta 1

Question 11

In the MHC class II molecule, what two domains have transmembrane regions that anchor the chains into the host cell membrane?

Answer 11

alpha 2 and beta 2

Question 12

What characteristic of MHC I and MHC II molecules makes them similar?

Answer 12

The alpha helices that make up the peptide binding domains and the alternating beta sheets that make up the floor of the peptide binding groove.

Question 13

What is the most important function of the MHC moletules?

Answer 13

To bind to peptides and present them to T cells

Question 14

T/F: MHC molecules bind to antigen peptides in a promiscuous fashion.

Answer 14

True

Question 15

T/F: MHC molecules bind to a limited number of peptides (they are very specific and picky).

Answer 15

False, remember, they are promiscuous! Sluts. MHC molecules are sluts.

Question 16

Regarding the MHC class I molecule’s peptide binding groove, how large of a peptide (in amino acids) will be accommodated by the groove?

Answer 16

peptides 8-10 amino acids in length

Question 17

What is the name for the amino acid residue with shared features among different peptides that will assist in locking the peptide into the peptide binding groove of the MHC molecule?

Answer 17

Anchor residue

Question 18

Do longer peptides bind to MHC class I or II molecules and why?

Answer 18

MHC class II. They have open ended peptide binding grooves that require a minimum of 13 AAs. The peptide will actually not fit completely within the binding groove.

Question 19

The MHC class I precessing and presentation pathway primarily presents antigens that are derived from intracellular or extracellular pathogens?

Answer 19

Intracellular pathogens

Question 20

The MHC class II precessing and presentation pathway primarily presents antigens that are derived from intracellular or extracellular pathogens?

Answer 20

Extracellular pathogens

Question 21

What is a proteosome?

Answer 21

A complex that takes up and degrades proteins that are targeted for destruction within the cytoplasm.

Question 22

What is the TAP transporter complex?

Answer 22

A complex that transports peptide products of the proteosome from the cytosol into the lumen of the ER.

Question 23

What is the significance of the TAP transporter complex in relation to immunology?

Answer 23

It participates in the process of loading peptides onto newly synthesized MHC class I molecules as it moves peptides (products of the proteosome) from the cytosol to the ER lumen.

Question 24

The TAP transporter complex associates with this complex that helps load the peptide from the proteosome onto the MHC molecule.

Answer 24

peptide-loading complex

Question 25

The TAP transporter can transport and assist in loading how many peptides at a time to the MHC with help of the peptide-loading complex?

Answer 25

One

Question 26

Are the MHC class I molecules stable if they have not been loaded with a peptide as they pass from the ER to the Golgi to the cell surface?

Answer 26

No.

Question 27

A deficiency of TAP transporter proteins will result in a person having very few cells that bear __________ on their surface.

Answer 27

MHC class I molecules

Question 28

In cells that are not antigen presenting to T cells but who do place MHC class I molecules with antigen peptides on their surface, what happens to them?

Answer 28

An effector T cell with specificity for that peptide can now potentially recognize the cell as an infected cell and effect its destruction via apoptosis.

Question 29

T/F: the vast majority of the peptides that are loaded onto MHC class I molecules are derived from pathogens.

Answer 29

False. The vast majority are derived from self proteins. Therefore, it is critical that all self-reactive T cells be removed from the T cell repertoire.

Question 30

Are MHC class II molecules loaded with cytosol-derived peptides as they are trafficked through the ER?

Answer 30

No.

Question 31

What blocks cytosolic peptides from loading into the MHC class II molecule?

Answer 31

The invariant chain protein. Part of this protein fits into the peptide binding groove of the MHC class Ii molecule and remains associated with the class II molecule until it has completed its passage through the ER and golgi app. and it resides in cytosolic vesicles. Once in the cytosolic vesicle, the invariant chain is cleaved leaving behind a short peptide called the CLIP fragment that continues the job of blocking cytosolic peptides.

Question 32

What provides the MHC class II molecule with an antigen peptide from the extracellular milieu for presentation to naive T cells?

Answer 32

a phagolysosome, containing materials collected from the extracellular milieu.

Question 33

The vast majority of all peptides ever loaded onto MHC class II molecules are derived from self or antigen proteins?

Answer 33

Self. Only during an infection will that be a source of non-self proteins for leading onto MHC class II molecules.

Question 34

Virtually all cells of the body express MHC class I except for these notable exceptions:

Answer 34

Erythrocytes- None

Neuronal cells- few

Question 35

MHC class II expression is restricted to ________________ .

Answer 35

professional antigen presenting cells

• dendritic cells
• B cells
• Thymic epithelium
• macrophages (some)

Question 36

CD4 T cells only recognize peptides bound to MHC class _____ proteins.

Answer 36

MHC class II proteins

Question 37

CD8 T cells only recognize peptides bound to MHC class ____ proteins.

Answer 37

MHC class I proteins.

Question 38

The primary role of the CD4 effector T cells is to:

Answer 38

Drive development of antibody responses

Question 39

__________ -mediated immune responses are usually the best for clearance of extracellular infections, and __________ T cells are required for priming acquired antibody responses.

Answer 39

antibody-mediated; effector CD4+ T cells

Question 40

Clearance of intracellular pathogens is mediated primarily by a ___ ____-mediated immune response.

Answer 40

T cell-mediated

Question 41

Intracellular pathogens’ antigenic peptides will be presented to ______ T cells by the MHC class ____ molecule.

Answer 41

CD8 T cells; MHC class I

Question 42

What is polygeny?

Answer 42

The existence in the genome of several different genetic loci encoding structurally similar proteins of identical function (isoforms).

Question 43

What is a polymorphism?

Answer 43

The existence of two or more forms (alleles) of a given gene within the population.

Question 44

T/F: both MHC class I and II expression is monogenic.

Answer 44

False. Both expressions are polygenic. The loci encoding MHC complex proteins are found in multiple genes.

Question 45

On each copy of chromosome 6 that a person inherits, there are (how many?) ____ loci that encode MHC class I molecules?

Answer 45

3. HLA-(A, B, C)

Question 46

On each copy of chromosome 6 that a person inherits, there are (how many?) _____ loci that encode MHC class II molecules?

Answer 46

3. HLA-(DP, DQ, DR)

Question 47

T/F: the MHC genes are the most polymorphic within the human genome.

Answer 47

True

Question 48

If a person inherits heterozygously at HLA-A, HLA-B and HLA-C, that person will express how many distinct isoforms of MHC Class I on all nucleated cells in their body?

Answer 48

6.

1 from each of 3 loci on each chromosome (2 total) inherited from mom & dad.

Question 49

Briefly describe the basis of transplant rejection.

Answer 49

Any particular person will only be tolerant to the MHC class I or MHC class II isoforms that they have inherited and express on their cells. Each person will have T cells in their repertoire that will recognize determinants derived from any MHC isoform that they do not express on their cells. Recognition by a T cell will initiate an immune response that is what we see clinically as “rejection”.

Question 50

Is it possible for alpha chains to pair with beta chains from a different locus?

Answer 50

No.

Question 51

Is it better to have a diverse array of isoforms of MHC class I & II?

Answer 51

Yes. The more isoforms you express, the higher the number of peptides that you will be able to present to naive T cells and the better your immune system will be at fighting infections.