antigen presentation 1

Question 1

t cell activation by antigens

Answer 1

dendritic cells take up the pathogen for degradation, the pathogen is taken apart inside the dendritic cell and its proteins are unfolded and cut into smaller pieces, peptides bind to MHC molecules and the complexes go to the cell surface
t cell receptors bind to peptide:MHC complexes on dendritic cell surfaces
these processed peptides can only be seen by t cells when displayed by MHC molecules
naive t cells are activated by MHC/peptide completexes presented by dendritic cells

Question 2

what is a major histocompatibility complex

Answer 2

a set of polymorphic genes found to control graft acceptance/ rejection due to immune response

Question 3

why dont mothers reject fetal tissue

Answer 3

no MHC1 is expressed

Question 4

what are the MHC class 1 isotypes

Answer 4

HLA A, B, C, D, E, F, G

E F and G dont present peptides to CD8 t cells

Question 5

what are the MHC class 2 isotypes

Answer 5

HLA DM, DO, DP, DQ, DR

DM and DO regulate peptide loading but dont present peptides

Question 6

MHC peptide binding motifs

Answer 6

2/3 anchor positions restrict the multiplicity of peptides that can be bound
class 1 MHC, positions 2 and 9 are usually restricted to 1 or 2 types
class 2 are variable in length so anchor proteins are harder to find

Question 7

advantages of polymorphisms in MHC

Answer 7

maintains diversity - proteins re processed into many component peptides
only a few will bind to a specific mhc molecule
to maximise net ability to bind peptides, individual HLA molecules exhibit significant diversity

Question 8

what is a haplotype

Answer 8

a combination of HLA alleles on chromosome 6

typical individuals have 6 diff antigen presenting MHC per chromosome

Question 9

what MHC do cd8 cells bind

Answer 9

alpha 3 domain of MHC class 1

Question 10

what MHC to cd4 bind

Answer 10

beta 2 domain of MHC class 2

Question 11

what type of cells are mhc class one presented in

Answer 11

all nucleated cells as any cell can be virally infected

Question 12

what type of cells are MHC class 2 presented in

Answer 12

only in cells that communicate with cd4 T cells

Question 13

what effect do cytokines produced during infection have on MHC expression levels

Answer 13

can increase MHC expression levels

Question 14

how do class 1 MHC molecules alert cells to intra cellular infection (VIRUSES)

Answer 14

the virus infect the cell, and viral proteins are synthesised in the cytoplasm
peptide fragments of viral proteins are bound to class 1 MHC in the ER
bound peptides are transported by MHC class 1 to the cell surface
cytotoxic t cells recognise the complex of the viral protein with MHC class 1 and kill the infected cells

Question 15

how do class 1 MHC molecules alert cells to extra cellular infection (BACTERIA)

Answer 15

macrophage engulfs and degrade the bacterium producing peptides
bacterial peptides bound to MHC class 2 in vesicles
bound peptides are transported by MHC class 2 . to cell surface
helper t cells recognise the complex of peptide antigen with the MHC class 2 and activate the macrophage
class 2 mhc is only expressed on dendritic cells, b cells and some macrophages
captures peptides to form endogenous antigens
displays them to t cells which express cd 4 coreceptor

Question 16

how do peptides bind to MHC

Answer 16

peptide side chains fit in pockets of MHC
NH2 and COOH termini of mhc class 1 peptides participate in bonding
n and c terminus in mhc class 2 do not

Question 17

mhc and peptide binding

Answer 17

mhc molecules display diverse pepties to t cells and a promiscuous peptide binders - thousands of peptides can bind to an individual mhc
key H bonds occur between peptide backbone and MHC side chains

Question 18

constraints of mhc and peptide binding

Answer 18

class 1 engages peptide termini hence length limit
c term amino acids in class 1 are usually basic or hydrophobic
some peptide chains fit into mhc pockets

Question 19

antigen presenting in class 1

Answer 19

peptide are produced in the cytosol and transported to the ER
the proteosome produces the 1st draft of peptides for class 1 sampling
INFy drive the expression of an alternate proteosome subunit to create an immunoproteosome able to produce peptides whose c termini meet class 1 binding requirements
peptides are delivered to the lumen by transporter associated with antigen processing

Question 20

how is class 1 assembly orchistrated

Answer 20

by peptide loading comlex
class 1 heavy chains stabilised by calnexin until next beta 2 microglobulin binds
calnexin is released and heterodimer of class 1 heavy chain and beta 2m forms peptide loading complex with calreticulin, tapasin ,tap, erp57 and PD1
a peptide delivereed by tap binds to class 1 heavy chain forming a mature class 1 molecule
class 1 molecule dissociates from the peptide loading complex and is exported from the ER

Question 21

what are the 1st draft peptides edited by

Answer 21

an aminopeptidase
the mhc class 1 is first edited by a peptide that is way too long at the n terminus
the aminopeptidase (ERAP)  then removes the n terminal amino acids to give a peptide of 8-10 residues 
the mhc class 1 molecule can . now travel to the cell surface