Adaptive Immune System- Antigen Processing and Presentation Flashcards
What is the major histocompatibility complex (MHC)?
A complex of genes that are major determinants of tissue compatibility during transplantation. Used to present antigen fragments to T cells and bind T cell receptors
Human: HLA
Mouse: H-2
What are the three types of MHC Class 1?
HLA-A, HLA-B, HLA-C
Give the expression of MHC Class 1
All nucleated cells in the body, APCs, platelets. Not on RBCs.
Give the function of MHC Class 1
Alerts CD8+ cytotoxic T cells to intracellular antigens
OR
Present endogenously synthesized antigens to CD8+ cytotoxic T cells
Give the structure of MHC Class 1
1 long chain, 1 short chain
Arranged as B C A
Give the structure of MHC class 2
2 equal length chains (2 α, 2 beta)
Arranged DP, DQ, DR
What is encoded within the MHC Class 3 region?
C4, Factor B, C2, Lymphotoxin, TNF α
Which features of MHC Class are what varies from one individual to another?
2 α-helices and beta sheet floor varies from one individual to another band between the different MHC molecules
What are non-polymorphic regions on the MHC important for?
The binding of other molecules to MHC (CD8 on 1, CD4 on 2)
What are pMHC?
Peptide MHC
A cell was destroyed by the immune system using the performing-granzyme pathway. What class of MHC is most likely to have signaled this T cell? How do you know?
MHC Class 1, because MHC 1 binds to CD8 on cytotoxic T cells
Give the function of MHC Class 2
Alerts CD4+ helper T cells and regulatory T cells to extra cellular antigens
OR
Present exogenously synthesized antigens to CD4+ helper T cells
Give the expression of MHC Class 2
Present on professional APCs (dendritic cells, macrophages, B cells) and on thymic epithelium
What are the three types of MHC Class 2?
HLA-DP, HLA-DQ, HLA-DR
Which human chromosome has the MHC?
Chromosome 6, inherited from mother
Which MHC chain is essentially non-polymorphic?
HLA-C β chain
Which sequence does not vary between individuals?
The HLA class 1 β chain gene
What is the associated protein of MHC Class 1?
β-2 microglobulin
In the MHC Class 1, which domains are polymorphic?
The α-1 and α-2 domains of the α chain.
Which MHC class 1 domain is closest to the transmembrane sequence?
The α3 domain
Which part of the MHC Class 1 molecule maintains the correct structural conformation of the α β heterodimer but doesn’t function in peptide binding?
β2- microglobulin
Which 2 locations can an antigen come from?
Endogenous
-processing of these antigens produce peptides that are 8-9 amino acids long
(MHC Class 1)
Exogenous
-processing of these antigens produce peptides that are approximately 15 amino acids long
(MHC Class 2)
What is TAP (TAP1 and TAP2)
Transporters associated with Antigen Processing
They pick up peptides as they’re being fed out of the end of the immunoproteasome and take them across the ER
What is the difference between the constitutive protein and the immunoproteasome?
The immunoproteasome is specialized to produce peptides of the length required to bind into MHC Class 1 groove
What do Tapasin, Calreticulin and Erp57 do?
They help keep the conformation of the MHC Class 1 correct for peptide binding
What is the molecule: invariant chain (Ii)
Acts as a stopper to prevent binding in the ER to the MHC Class 2
What is the remaining part of the invariant chain called?
CLIP
What does DM and DO do?
They remove CLIP and insert the peptide into the peptide binding groove
Why is ubiquitination an important part of antigen processing?
It marks the protein so that the proteasome can recognize it
A patient has a functional genetic defect in the area of a genome that encodes for the TAP1 and TAP2 molecules. At a molecular level, what would this patients cells not be able to do?
Transport processed peptides out of the cytosol, through the ER, to be presented by the MHC Class 1 molecule
Discuss cross presentation
The endogenous and exogenous pathways are not completely separated.
Endogenous antigens can enter the MHC Class 2 and be presented to CD4+ helper and regulatory T cells.
Exogenous antigens can enter the MHC Class 1 and be presented to CD8+ cytotoxic T cells
When does the term cross presentation apply?
Exogenous antigens are presented by MHC Class 1
