L11, MHC and Antigen Presentation

Question 1

recap: what is antigen presentation and what is the significance of it?

Answer 1

antigen presentation is the process by which an antigen located on the surface of an APC (e.g., a macrophage), is presented to a naive T-cell

Question 2

what are MHC proteins?

Answer 2

cell surface glycoproteins (except MHC-III) that bind antigens and display them to T cells bearing the appropriate TCR

Question 3

function of MHC-I

Answer 3

presentation of cytosolic antigens to CD8+ cytotoxic T cells (Tc)

Question 4

function of MHC-II

Answer 4

presentation of extracellular/vesicular antigens to CD4+ T helper cells (Th)

Question 5

function of MHC-III

Answer 5

secreted proteins; not involved in antigen presentation to T cells. includes complement, innate immune cytokines

Question 6

what are MHC gene products referred to in humans?

Answer 6

HLA (Human Leukocyte Antigens)

Question 7

what are MHC gene products referred to in mice?

Answer 7

H2

Question 8

what cells are MHC-I molecules expressed by?

Answer 8

nearly all nucleated cells of the body

Question 9

what antigens does MHC-I present?

Answer 9

• endogenous antigens (derived from intracellular pathogens)
• exogenous antigens by cross-presentation (mostly done by DC cells)

Question 10

what does the presentation of self-peptide on MHC-I mean?

Answer 10

that a cell is healthy and should not be targeted by CD8+ cytotoxic T cells

Question 11

what does MHC-I gene encode?

Answer 11

a single alpha chain protein

Question 12

what MHC-II molecules mostly expressed by?

Answer 12

professional antigen presenting cells (pAPCs)

Question 13

what are the three pAPCs?

Answer 13

Dendritic cells, macrophages, B cells

Question 14

what antigens do MHC-II present?

Answer 14

exogenous antigens (extracellular) to CD4+ T helper cells

Question 15

what does each MHC-II gene encode?

Answer 15

both single alpha and beta chains

Question 16

what are the three membrane-distal domains of MHC-I?

Answer 16

alpha 1,2,3 and Beta-2 microglobulin

Question 17

what are the three membrane-distal domains of MHC-II?

Answer 17

alpha 1, alpha 2, beta 1, beta 2

Question 18

define polygeny

Answer 18

multiple alleles

Question 19

why is MHC diversity so great?

Answer 19

because of polymorphism within multiple alleles from one individual to another

Question 20

polygeny + polymorphism = ….

Answer 20

great diversity

Question 21

MHC genes are …. and exist in an individual and are …. expressed

Answer 21

polygenic
codominantly

Question 22

what does a mismatch of HLA haplotypes lead to?

Answer 22

graft rejection

Question 23

what does antigen processing lead to?

Answer 23

the degradation of the antigen into small antigenic peptides

Question 24

what is the MHC-I peptide loading process?

Answer 24

1. endogenous antigen is degreaded by the proteasome to yield small antigenic peptides
2. peptides are transported into the endoplamic reticulum via TAP
3. Calreticulin and tapasin bind to the MHC-I molecule, catalyzing the removal of the chaperone and binding of the antigenic peptide
4. peptide-loaded MHC-I molecules are eventually brought to the cell surface

Question 25

what is the MHC-II peptide loading process?

Answer 25

1. invariant chain binds the MHC-II groove to prevent binding of endogenous peptides
2. MHC-II-li complex traffics through the endocytic pathway
3. within acidified endosomal and endolysosomal compartments, antigens are broken down with the help of proteases into small antigenic peptides (13-18 amino acids)
4. the same proteases will degrade the invariant chain, leaving only a small fragment (CLIP) in the groove of the MHC-II molecule
5. CLIP is removed and replaced by the antigenic peptide
6. peptide-loaded MHC-II molecules are eventually brought to the cell surface

Question 26

what happens during MHC-I cross presentation

Answer 26

1. exogenous antigens are internalized by APC
2. antigenic peptides are presented to CD4+ Th cells by MHC-II molecules
3. antigen-activated Th cells then “license” DCs to present these antigens but on MHC-I molecules
4. this activates CD8+ Tc cells

Question 27

what cells are predominantly responsible for antigen cross-presentation?

Answer 27

dendritic cells