MHC Structure and function

Question 1

HLA or human leukocyte antigen refers to which structures?

Answer 1

MHC molecules

Question 2

Name the two sets of polymorphic genes found on MHC loci.

Answer 2

MHC I

MHC II

Question 3

Describe the structure of an MHC I protein including the bond between the chains.

Answer 3

3 alpha chains and 1 beta-2 microglobulin
alpha 1 and alpha 2 form the binding cleft/groove
beta-2 microglobulin and alpha 3 form
the alpha 3 binds the CD8 coreceptor (NOT CD4!!!)
The b-2 microglobulin is bound noncovalently to the alpha chain
The upper 2 subunits are polymorphic
the lower 2 subunits are not polymorphic

Question 4

General structure of an MHC molecule

Answer 4

4 subunits (may consist entirely of alpha chains or include a beta-2 microglobulin chain)
The upper 2 subunits form the binding cleft/groove
The binding cleft is made of amino acids
The floor of the binding cleft binds the antigen
The walls of the binding cleft will bind to the coreceptor
the lower subunits will bind the T cell coreceptor

Question 5

What are the reasons for someone having high levels of Antibodies? [3]

Answer 5

Multiparous (given birth multiple times)
Multiple transfusions
Multiple grafts/transplants

Question 6

What are the properties of MHC genes? [4]

Answer 6

1. Highly polymorphic
2. Polygenic (different non-allelic genes involved)
3. Co-dominantly expressed
4. Have pleiotropic functions (produce more than one effect)

Question 7

How many alleles of MHC class I loci do you get from each parent?

Answer 7

3
HLA-A
HLA-B
HLA-C

Question 8

Define MHC haplotype

Answer 8

set of MHC alleles present on each chromosome

Question 9

MHC proteins can only bind peptides in which location?

Answer 9

Inside the cell during their synthesis and transport

Question 10

What is one necessary condition for MHC molecules to be expressed on the cell surface?

Answer 10

they must already have a bound peptide

Question 11

Can MHC molecules discriminate between self and non-self?

Answer 11

No

Question 12

If MHC molecules are constantly displaying self-antigens, why does autoimmunity not occur?

Answer 12

because the t lymphocytes reactive to self antigens are destroyed or inactivated

Question 13

What is the purpose of segregating antigen processing pathways? Which pathway occurs in which compartment?

Answer 13

The purpose is to allow sampling of peptides from both intracellular and extracellular compartments. 
The class I MHC pathway is for intracellular components in the cytosol. 
The class II MHC pathway is for exracellular proteins.

Question 14

which DNA typing method is used for HLA typing?

Answer 14

southern blot - using electrophoresis separated DNA fragments, filtering them via a filter membrane, and detecting them via probe hybridization

Question 15

which serological typing method was used for HLA typing?

Answer 15

MLR (mixed lymphocyte reaction)

Question 16

MHC I molecules are expressed in all nucleated cells except?

Answer 16

RBCs

Trophoblasts of placenta

Question 17

On which cell types do MHC II molecules tend to expressed?

Answer 17

Macrophages
Dendritic cells
B lymphocytes
(basically APCs)

Question 18

The MHC III gene encodes for which molecules?

Answer 18

Complement
Heat-shock proteins
Cytokines

Question 19

What are the two parallel nomenclatures used in identifying MHC alleles?

Answer 19

Serological (based on Ab’s) - lower resolution

Parallel (based on DNA testing) - uses * to identify specific alleles so has higher resolution

Question 20

Which kind of antigens are recognized by T lymphocytes versus B lymphocytes?

Answer 20

T lymphocytes only recognize protein antigens

B lymphocytes can recognize in addition polysaccharides, lipids, and nucleic acids

Question 21

Define MHC restriction

Answer 21

A property of T lymphocytes that refers to their limited capability to only recognize MHC-bound antigens.

Question 22

Name the most specialized and efficient APC.

Answer 22

Dendritic cells

Question 23

How would a rare lymphocyte for a microbial agent find that microbe, considering that microbes can enter anywhere in the body?

Answer 23

The microbe is taken up by a dendritic cell and transported to a lymphoid organ through which lymphocytes are constantly recirculating

Question 24

the two major types of dendritic cells as well as their locations.

Answer 24

classical (in tissues and lymphoid organs)and plasmacytoid (in blood and tissues)

Question 25

Which dendritic cell is a major source of IFN-1?

Answer 25

plasmacytoid

Question 26

How are dendritic cells activated?

Answer 26

The foreign microbe binds to pattern recognition receptors (ex: TLRs) on macrophages, epithelial cells, and DCs. causes release of cytokines like TNF and IL-1/
these cytokines in turn activate dendritic cells

Question 27

What is the binding cleft size of MHC-I? MHC-2?

Answer 27

MHC I - 8-11 residues

MHC 2 - 10-30 residues

Question 28

Strategies used by viruses to block the class I MHC molecular pathway. [3]

Answer 28

1. Removing newly synthesized MHC molecules from ER
2. Inhibit transcription of MHC genes = no MHC production
3. block peptide transport by TAP