antigen presentation 1 Flashcards
t cell activation by antigens
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
what is a major histocompatibility complex
a set of polymorphic genes found to control graft acceptance/ rejection due to immune response
why dont mothers reject fetal tissue
no MHC1 is expressed
what are the MHC class 1 isotypes
HLA A, B, C, D, E, F, G
E F and G dont present peptides to CD8 t cells
what are the MHC class 2 isotypes
HLA DM, DO, DP, DQ, DR
DM and DO regulate peptide loading but dont present peptides
MHC peptide binding motifs
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
advantages of polymorphisms in MHC
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
what is a haplotype
a combination of HLA alleles on chromosome 6
typical individuals have 6 diff antigen presenting MHC per chromosome
what MHC do cd8 cells bind
alpha 3 domain of MHC class 1
what MHC to cd4 bind
beta 2 domain of MHC class 2
what type of cells are mhc class one presented in
all nucleated cells as any cell can be virally infected
what type of cells are MHC class 2 presented in
only in cells that communicate with cd4 T cells
what effect do cytokines produced during infection have on MHC expression levels
can increase MHC expression levels
how do class 1 MHC molecules alert cells to intra cellular infection (VIRUSES)
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
how do class 1 MHC molecules alert cells to extra cellular infection (BACTERIA)
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
how do peptides bind to MHC
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
mhc and peptide binding
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
constraints of mhc and peptide binding
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
antigen presenting in class 1
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
how is class 1 assembly orchistrated
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
what are the 1st draft peptides edited by
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