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Flashcards in MHC Deck (39):
1

What is the Major Histocompatability Complex?

•  a large cluster of genes encoding specialized glycoproteins;  many functions

2

What is the most important role of MHC?

 ••  role in antigen presentation to T cells  ••

3

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

true

4

Of the MHC I characteristics, which is the same throughout all individuals

B2- microglobulin

5

Describe peptide binding of MHC 

  • each MHC molecule (class I or class II) can bind to many different peptides
  • MHC class I and class II molecules do have slightly different peptide-binding characteristics

6

Describe the binding cleft of MHC class I molecules

 is closed

7

Compared to MHC I, the ability of MHC II to bind to peptides is what?

less restrictive

8

 the binding cleft of MHC class I molecules is closed and will only bind to peptides with what length of AA?

 between 8-10 amino acids in length

9

Peptide binding to MHC I is stabilized how?

stabilized by contacts between the aminoterminal and carboxyterminal ends of the peptide and invariant sites found at the ends of the binding grooves

10

Describe the binding cleft of MHC II

the binding cleft of MHC class II molecules is open;

the ends of  the peptide can hang over the edge of the cleft

11

MHC II will bind peptides of what length?

will bind to peptides at least 13 amino acids in length,   and can be much longer

12

How is MHC II stabilized?

peptide binding is stabilized by contacts between the    peptide backbone and conserved residues that line the MHC class II binding groove

13

MHC Class I Ag-Processing and Presentation Pathway (4 steps)

  1. class I HC is stabilized by calnexin until B2-microglobulin binds
  2. calnexin released and heterodimer of class I HC and B2-mg forms peptide-loading complex with clareticulin, tapasin, TAP, ERp57, and PDI
  3. peptide delivered by TAP binds to class I HC, forming mature MHC I molecule
  4. class I molecule dissociates from the peptide-loading complex, and is exported from the ER

14

What is step 1 of MHC Class I Ag-Processing and Presentation Pathway?

class I HC is stabilized by calnexin until B2-microglobulin binds
 

15

What is step 2 of MHC Class I Ag-Processing and Presentation Pathway?

calnexin released and heterodimer of class I HC and B2-mg forms peptide-loading complex with clareticulin, tapasin, TAP, ERp57, and PDI
 

16

What is step 3 of MHC Class I Ag-Processing and Presentation Pathway?

peptide delivered by TAP binds to class I HC, forming mature MHC I molecule
 

17

What is step 4 of MHC Class I Ag-Processing and Presentation Pathway?

class I molecule dissociates from the peptide-loading complex, and is exported from the ER

18

Describe the antigen presentation to T cells wrt to MHC I

  1. intracellular antigen processing to peptides in proteasome
  2. peptide transport into ER
  3. peptide binding by MHC I
  4. MHC I presents peptide at cell surface

19

Describe the MHC Class II Ag-Processing and Presentation Pathway (4 steps)

  1. invariant chain blocks binding of peptides to MHC II molecules in ER
  2. in vesicles invariant chain is cleaved, leaving the CLIP fragment bound
  3. CLIP blocks binding of peptides to MHC II in vesicles
  4. HLA-DM facilitates release of CLIP, allowing peptides to bind

20

What is step 1 of MHC Class II Ag-Processing and Presentation Pathway?

invariant chain blocks binding of peptides to MHC II molecules in ER
 

21

What is step 2 of MHC Class II Ag-Processing and Presentation Pathway?

in vesicles invariant chain is cleaved, leaving the CLIP fragment bound
 

22

What is step 3 of MHC Class II Ag-Processing and Presentation Pathway?

CLIP blocks binding of peptides to MHC II in vesicles
 

23

What is step 4 of MHC Class II Ag-Processing and Presentation Pathway?

HLA-DM facilitates release of CLIP, allowing peptides to bind

24

describe Antigen Presentation to T Cells wrt to MHC class II

  1. extracellular antigen endocytosed
  2. peptide production in phagolysosome 
  3. peptide binding  by MHC II
  4. MHC II presents peptide at cell surface

25

Describe how MHC molecules present peptides to T cells

CD4 T cells recognize peptides bound to MHC class II

CD8 T cells recognize peptides bound to MHC class I
 

26

What is the Significance of MHC Distribution? (2)

•  MHC molecules present peptides to T cells

•  immune response is “tailored” to the type of infection

27

Describe how immune response is “tailored” to the type of infection

Ab-mediated immune responses best for clearance of    extracellular pathogens

T cell-mediated immune responses are best for     clearance of intracellular pathogens

28

What is the existence in the genome of several different genetic loci encoding structurally similar proteins of identical function (isoforms)?

polygeny

29

What is the existence of two or more forms (alleles) of a given gene within the population (variant alleles occur at a frequency of at least 1%)?

Polymorphism (genetic)

30

Describe the genes MHC I inherited

3 MHC class I gene on each chromosome

  • HLA-A
  • HLA-B
  • HLA-C

31

Describe the genes MHC II inherited

each person inherits at least 3 MHC class II genes on each chromosome

  •  HLA-DP
  • HLA-DQ
  • HLA-DR (either 1 or 2 on each chromosome)

32

T/F MHC expression is what?

polygenic

33

Describe the minimum number of MHC molecules expressed/person (both classes)

3 different MHC class I molecules

3 different MHC class II molecules

34

What is •  maximum number of MHC molecules expressed/person? (both classes)

6 different MHC class I molecules


48 different MHC class II molecules

35

any tissue bearing non-self MHC will be rejected. Why?

T cell-mediated immune response

MHC in Transplant Rejection

36

What is a transplant between genetically identical individuals? 

syngeneic transplant (isograft)

37

What is a transplant between genetically different individuals?

allogeneic transplant (allograft)

38

What is a transplant of tissue from a different species?

zenograft

39

Describe what is necessary before a bone marrow transplant and what occurs after

bone marrow transplant:  host immune system is   destroyed prior to transplant

following transplant, mature T cells (from transplant) attack allogeneic tissue of the host