MHC Genomic Organization and Structure

Question 1

Characteristics of each class of genes that code for MHC

Answer 1

1. Class I MHC genes encode glycoproteins expressed on the surface of nearly all nucleated cells. Function: presentation of peptide antigens to Tc cells.
2. Class II MHC genes encode glycoproteins expressed primarily on antigen-presenting cells (macrophages, dendritic cells, B cells), where they present processed antigenic peptides to Th cells. Thymic Epithilial Cells (TEC)
3. Class III MHC genes encode secreted proteins that have immune functions s.a Complement system and molecules involved in inflammation.

Question 2

How do Class I AND Class II structures differ?

Answer 2

Class I

• Peptide binding cleft
• 1 chain (a1, a2, and a3) and a Beta2 microglobin molecule
• I transmembrane segment
• Anchors molecules at both ends of the peptide;generally hydrophobic carboxy-terminal anchor

Class II

• Open socket for peptide binding
• Two chains (a and b)
• 2 Transmembrane segments
• Conserved residues along the length of the peptide

Question 3

Bare Lymphocyte Syndrome I

Answer 3

Tap 1 and 2 deficiences

Prevents the formation of peptide : HLA I complex

HLA class I not expressed on the membrane

Question 4

CIITA (class II transactivator)

Answer 4

a protein that interacts with and stabilizes the RFX complex but does not bind to the MHC class II gene promoter itself.

Question 5

How many amino acids are found in the alpha chains of the MHC Class I molecule?

Answer 5

Approximately 90

Question 6

What is the nature of the bound peptide in MHC Class I? Class II?

Answer 6

Class I (Extended structure in which both ends interact with the MHC molecule but the middle arches away from the MHC molecule

Class II (Extended structure that is held in constant elevation above the floor of the MHC groove

Question 7

What type of inheritance does MHC express?

Answer 7

Codominance

Question 8

Regions and Gene Products of CLASS II

Answer 8

Regions: DP, DQ, DR

Gene Products: DP alphabeta, DQ alphabeta, DR alphabeta

Question 9

Mutations of which genes can cause BLS II?

Answer 9

RFX

CIITA

Question 10

MHC genes are highly ______________

Answer 10

polymorphic.

Question 11

When can T cells recognize an antigen?

Answer 11

Once it has been processed and presented in the context of molecules encoded by MHC

Question 12

The MHC is referred to as the _________ complex in humans and the _________ complex in mice.

Answer 12

HLA; H-2

Question 13

Allelic forms of MHC genes are inherited in linked groups called ____________

Answer 13

haplotypes.

Question 14

In which order are gene classes expressed on the HLA complex?

Answer 14

II, III, I

Question 15

The major histocompatibility complex is a collection of genes arrayed within a long continuous stretch of DNA on chromosome__________ in humans and on chromosome_________ in mice.

Answer 15

6; 17

Question 16

Class II MHC molecules contain two different polypeptide chains, a ____________ α chain and a ___________ β chain, which associate by ___________interactions

Answer 16

33-kDa; 28-kDa; noncovalent

Question 17

The ability of an individual class I MHC molecule to bind to a diverse spectrum of peptides is due to ____________

Answer 17

the presence of the same or similar amino acid residues at key positions along the peptides.

Question 18

Regions and Gene Products of CLASS I

Answer 18

Regions: B,C,A

Gene Products: HLA-B, HLA-C, HLA-A

Question 19

Wat four factors regulate MHC expression?

Answer 19

1. Transcription factors
2. Cytokines
3. Interferon Gamma :induce the formation of a specific transcription factor that binds to the promoter sequence flanking the class I and II MHC genes
4. IL-4; Increases expression of class II molecules by resting B cells.

Question 20

_____________molecules expressed by an individual influences the repertoire of antigens to which that individual’s T cells can respond

Answer 20

MHC

Question 21

RFX (regulatory factor X)

Answer 21

forms a complex that binds to the promoter of the MHC class II gene; the fourth factor

Question 22

Role of MHC

Answer 22

1. Play roles in intercellular recognition and in discrimination between self and nonself.
2. Participates in the development of both humoral and cell-mediated immune responses.

Question 23

What are the clinical manifestations of BLS?

Answer 23

• infections of the respiratory or the digestive tract.
• Absence of antibody formation and the absence of cell-mediated response.
• Necrotizing granulomatous skin lesions.
• Chronic inflammation of the upper respiratory tract include lethal midline granuloma (LMG)
• Chronic sarcoidosis

Question 24

Nonclassical gene products

Answer 24

Expression of the class I HLA-G molecules on cytotrophoblasts at the fetal-maternal interface.

HLA-G may play a role in immune tolerance in pregnancy.

HLA-G is a ligand for NK cell inhibitory receptor KIR2DL4, and therefore expression of this HLA by the trophoblast defends it against NK cell-mediated death

Question 25

Bare Lymphocyte Syndrome II

Answer 25

Mutation in genes that regulate the expression of MHC II genes

Treatment: Bone marrow transplantation

Question 26

Regions and Gene Products of CLASS III

Answer 26

Region: C4, C2, BF

Gene Products: C- Proteins, TNFa, TNFbeta

Question 27

Which MHC class includes complement proteins?

Answer 27

MHC Class III

Question 28

•The α1 and α2 domains interact to form a platform of _________ antiparallel β strands spanned by ________long α-helical regions.

Answer 28

eight;two

Question 29

Both class I and class II MHC genes are flanked by 5’ promoter sequences that bind____________

Answer 29

transcription factors

Question 30

•Class I MHC molecules contain a____________ (kDa) α chain associated noncovalently with a __________β2-____________ molecule.

Answer 30

45-kilodalton; 12-kDa; microglobulin

Question 31

Amino acids at positions ______,________ and ___________ are considered anchor residues.

Answer 31

2, 3, and 9

Question 32

What size peptide can bind to the cleft of MHC class II molecules?

Answer 32

13-18 aa

Question 33

The peptide-binding region is located on the surface of the MHC I molecule and is able to bind a peptide of _________ to _________amino acids.

Answer 33

8;10