MHC/HLA Structure, Function, and Genes

Question 1

Histocompatibility gene products are responsible for what reactions?

Answer 1

Transplantation rejection reactions

Question 2

the particular set of MHC molecules a person expresses will affect?

Answer 2

the repertoire of antigens to which that person’s T cells can respond

Question 3

Where are the MHC genes located in mice?

Answer 3

in the H-2 complex

Question 4

what is HLA

Answer 4

human leukocyte antigen

Question 5

Where are the genes for HLA located in humans?

Answer 5

in the HLA complex

Question 6

what genes code for the class I MHC in humans and mice

Answer 6

mice: H-2 K and D (codes for H2-L and H2-D) regions

Humans: HLA A, B, C regions

Question 7

what genes code for Class II MHC in humans and mice

Answer 7

Mice: H-2 I (IA, IE)

Humans HLA D (DP, DQ, DR)

Question 8

Where are class I MHC molecules present?

Answer 8

Nearly all nucleated cells

Question 9

What is the function of class I MHC?

Answer 9

to present non-self peptide antigens

• usually derived from endogenous (intracellular) proteins
• present to CD8+ cytotoxic T lymphocytes

Question 10

Where are class II MHC molecules generally expressed

Answer 10

primarily on antigen presenting cells

• present non-self peptide antigens usually derived from exogenous (extracellular) proteins that have been phagocytised
• present to CD4 helper T cells

Question 11

What are class III MHC molecules?

Answer 11

Soluble gene products that are associated with immune responses (e.g., complement proteins and TNF α and β)
-not directly involved in T cell recognition of antigen

Question 12

General structure of the class I MHC molecule

Answer 12

polymorphic 45 kDa transmembrane peptide alpha chain noncovalently linked to an invariant 12 kDa β2 microglobulin molecule

Question 13

What is the organization of the class I MHC α chain

Answer 13

• 3 globular domains that are external to the cell (α1, 2, and 3)
• hydrophobic sequence (membrane anchor)
• short hydrophilic sequence (in the cytoplasm)

Question 14

α1 and α2 domains form what important feature of the molecule? What is the secondary structure of this feature?

Answer 14

the cavity that is occupied by an antigen in the form of a linear peptide

Formed by 2 alpha helices on a ß-pleated sheet

*closed at both ends

Question 15

How long can the peptide be that binds to the class I MHC receptor ?

Answer 15

8-10 amino acids

Question 16

What is the function of the α3 domain?

Answer 16

Highly conserved.

Interacts with the ß1 microglobulin as well as with the CD8 co-receptor on cytotoxic T cells

Question 17

What food can you compare the class I MHC receptor to?

Answer 17

A pita where the antigen is the filling

Question 18

What kind of interactions mediate the contact between peptide antigen and the class I MHC? What is the binding like between the antigen and the receptor?

Answer 18

hydrogen bonds

Anchor residues at both ends of the peptide that interact with the MHC groove but middle arches up and away from the MHC molecule

Question 19

What is the difference between short and long peptides binding in the groove?

Answer 19

longer peptides bulge in the middl where shorter peptides lie flat

Question 20

general structure of class II MHC molecules ?

Answer 20

polymorphic 33kDa α (1 and 2) and 28kDa β (1 and 2) transmembrane peptide chains which associate by noncovalent interactions.

Question 21

What is the organization of each of the α and β chains in class II MHC?

Answer 21

they each have external globular domains, a hydrophobic membrane anchor, and a short hydrophilic cytoplasmic tail.

Question 22

Which 2 domains form the antigen binding cleft in class II MHC?

Answer 22

α1 and β 1 domains form the antigen-binding cleft

Open at both ends

Question 23

the antigen binding cleft of class II MHC can hld peptides up to how long?

Answer 23

13-18 AA

Question 24

How does the peptide interact with the antigen binding cleft of class II MHC?

Answer 24

via hydrogen bonds that form between the backbone of the peptide and the cleft of the class II MHC molecule
-peptide lies fairly flat

Question 25

What food group can be used to describe the antigen binding cleft in class II MHC

Answer 25

A hotdog bun and the antigen is the hot dog

Question 26

What is an MHC polymorphism and where does it occur in each of the classes?

Answer 26

Differences exist between individuals in the amino acid sequences of the α1 and α2 domains of class I MHC molecules, and the α1 and β1 domains of class II MHC molecules at the sites that form the β- pleated sheet floor and the inner surfaces of the α- helices.

Question 27

What does polymorphism within a population ensure

Answer 27

that an enormous number of antigenic peptides can be presented to T cells by MHC molecules.

Question 28

an y given MHC molecule can bind ____ different peptides

Answer 28

many

Question 29

Whats is an MHC haplotype?

Answer 29

denotes the set of allelic form of H-2 (for class I and II MHC) genes expressed by  particular strain of mice 
-designated by an arbitrary superscript

ex: if a mouse is haplotype k, then for all the H-2 alleles it will be k

Question 30

Where is the highest level of class 1 MHC found?

Answer 30

on lymphocytes

Question 31

Which cells express the lowest levels of class I MHC?

Answer 31

muscle cells and neural cells

Question 32

Which cells lack class I MHC all together?

Answer 32

Neurons

Question 33

How and where are class II MHC molecules expressed?

Answer 33

Expressed constitutively on professional antigen presenting cells only

-macrophages will increase their level upon activation

Question 34

Which 2 types of cells can be induced to express class II MHC

Answer 34

epithelial cells and endothelial cells

Question 35

on which chromosome is the mouse H-2 region located?

Answer 35

17

Question 36

on which chromosome is the HLA region located?

Answer 36

6

Question 37

How is expression of class I and II MHC GENES controlled?

Answer 37

by transcription factors

Question 38

How is expression of class I and II MHC on cells controlled?

Answer 38

Cytokines such as interferon-γ

Question 39

MHC gene inheritance and expression is…?

Answer 39

codominant

Question 40

what does codominance mean in terms of MHC?

Answer 40

MHC molecules encoded by both parental genes are expressed on a single cell

Question 41

What does the heterozygosity confer?

Answer 41

increases the number of different peptides that can be presented by MHC molecules.

Question 42

Immune responsiveness to exogenous antigens is under the control of which class of MHC?

Answer 42

class II

Question 43

What is the determinant selection model?

Answer 43

Different allelic forms of class II MHC molecules differ in their ability to bind processed antigen.

Question 44

what is the holes in the repertoire model?

Answer 44

T cells bearing T cell receptors that recognize foreign antigens that closely resemble self-antigens have been eliminated during thymic development.
-negative selection

Question 45

Variations in what can determine the effectiveness of the immune response?

Answer 45

antigen presentation by different MHC alleles

Question 46

What tends to happen if the major epitopes of a pathogen mimic certain self-antigens?

Answer 46

the individual is likely to lack functional T cells that are specific for the pathogen

Question 47

A reduction in MHC polymorphism may predispose a species to what?

Answer 47

disease by limiting the range of processed antigen that can interact with MHC molecules