L6: Major Histocompatibility Complex Flashcards Preview

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Flashcards in L6: Major Histocompatibility Complex Deck (40)
1

What do T cells recognize?

Processed antigen fragments presented by MHC molecules

2

What do helper CD4+ T cells recognize?

Processed antigen fragments presented by MHC class II molecule

3

What do cytotoxic CD8+ T cells recognize?

Processed antigen fragments presented by MHC class I molecule

4

What gene complex encodes the MHC proteins in humans?

Human leukocyte antigen (HLA)

5

What loci is human MHC Class I encoded by?

Loci HLA-A, HLA-B, and HLA-C

6

What loci is human MHC Class II encoded by?

HLA-DR, DQ, and DP

7

What are some other genes mapped within the MHC region?

Factor B
Complement proteins
TAP1 and TAP2
Cytokine genes (such as TNF)
Some non-classical MHC class I genes: HLA-E, HLA-F, and HLA-G

8

What are the 2 striking characteristics of the MHC system?

1. Extremely polymorphic: at each of the loci, there are numerous alternative alleles

2. These, as far as expression of HLA molecules on surface of cells that express them, will be co-dominantly expressed

9

What is the inheritance pattern of HLA?

Standard Mendelian segregation
Recombination can occur

10

In MHC Class I, which loci is most polymorphic?

B

11

In MHC Class II, which loci is most polymorphic?

DRB

12

Describe the general structure of MHC Class I molecules

Heavy α
chain that is non-covalently associated w/ small chain called β-2 microglobulin

13

What aspect of MHC class I molecules is invariant?

β-2 microglobulin

α3 domain

14

What forms the peptide binding cleft in MHC class I molecules?

α1 and α2 domains

15

Where on MHC class I does the receptor recognize it?

α3 domain

16

Describe the general structure of MHC class II

2 heavy chains: an α chain and a β chain

17

What forms the peptide binding cleft in MHC class II molecules?

α1 and β1 regions

18

At any given time, how many peptides can a peptide binding cleft bind?

1 peptide

19

What is the nature of the peptide-binding cleft of MHC class I molecules? Class II molecules?

Class I: closed at both ends

Class II: open at both ends

20

What is the general size of bound peptides of MHC class I molecules? Class II molecules?

Class I: 8 - 10 amino acids (9 is ideal)

Class II: 13 - 18 amino acids

21

What are the peptide motifs involved in bind to MHC class I molecule? Class II molecule?

Class I: Anchor residues at both ends of peptide; generally hydrophobic carboxyl-terminal anchor

Class II: Anchor residues distributed along the length of the peptide

22

What allows MHC class II molecules to bind larger peptides?

Peptide binding cleft is open

23

What has to be the same in all the peptides that can bind a specific MHC class I molecule?

The anchor residues must be the same for them to bind the same MHC class I molecule

24

What are the anchor residues of MHC class I molecules?

2 and 8 positions

25

What are the anchor residues of MHC class II molecules?

Anchor residues not so well defined

26

Where does allelic variation occur within MHC molecules?

In peptide binding pockets

For class I, variation is found in alpha 1 and apha 2 domains (alpha 3 is invariant)

For class II, variation is found mostly in beta 1 domain

27

How is T cell recognition of antigens restricted?

It is MHC restricted

T cell receptor has a specific recognition area that will bind self-MHC that some processed peptide

Both the peptide and the MHC molecule need to be correct for recognition to occur

28

Where are MHC class I molecules distributed (in humans)?

All nucleated cells
Platelets
Not on RBCs (which is fortuitous in blood transfusion)

29

Where are MHC class II molecules distributed (in humans)

Primarily on cells that can act as antigen-presenting cells

B cells
Macrophages
Dendritic cells
Activated T cells (human)

30

Are all cells that express class II molecules also going to express class I molecules?

Yes

31

Are all cells that express class I molecules going to express class II molecules?

Not necessarily

32

What is the exception to the rule of T cells only recognizing self-MHC w/ some foreign antigenic peptide attached to it?

T cell alloreactivity

33

T cell alloreactivity

Ability of T cell in culture dish or in vivo (in certain conditions) to recognize foreign, or non-self, MHC

Only time this could happen in vivo is in case of organ transplantation where organ is of different MHC than you are

Could also happen during a blood transfusion if WBCs are part of blood product that you receive

Or during pregnancy

This is the basis of what happens in graft rejection

34

What are the situations in which allogenic T cell reactivity occurs in vivo?

Organ transplant

Blood transfusion if WBCs are part of the blood product

During pregnancy

35

Superantigen

Don't bind in the antigen binding groove

Bind on the outside of the antigen presenting cell

Many different T cells can bind to a self-MHC that has either a bacterial or viral superantigen that is attached to it

36

Why is high level of MHC polymorphism advantageous?

Most human MHC molecules are expressed at pretty low frequency since there are so many different ones that can bind different antigenic peptide

If there was limited expression of MHC, there would be limited binding of those viruses and thus there would be limited response

37

How is serological tissue typing done?

Use HLA molecules since they are expressed on WBCs and you can detect them serologically; have antibodies to almost all of the different alleles that are found

Take a donor cell and put it in a dish w/ an antibody to a certain HLA allele → if there is that HLA allele, there will be formation of antigen-antibody complex → add complement → cell membrane lysis if there is antigen-antibody complex → add dye → if there was membrane lysis, the dye is taken up by the cell → if dye was taken up, tells us that this cell expressed that HLA allele

38

MHC typing by PCR hydbridization

Same concept as serological testing, but more sensitive and quicker

39

Mixed lymphocyte reaction

To measure alloreactivity

40

What is the effect of HLA class I and class II matching on allograft survival?

If there are no mismatches at MHC class I and II molecules b/w recipient and donor, have much higher survival rate of graft

As you increase the # of mismatches, survival rate decreases