4. Major Histocompatibility complex Flashcards
Major Histocompatibility Class (MHC) II
Function:
to present peptide antigens
Major Histocompatibility Complex
MHC Class I & II (and III)
Human Leucocyte Antigen (HLA) main classes: - HLA - A, B, C = MHC Class I - HLA - DR, DP , DQ = MHC Class II - MHC Class I present on nucleated cells of body
How many MHC molecules does a cell express?
MHC Class I – probably 6
- co-dominant expression of paternal and
maternal HLA – A, B & C loci
NB - Minor Histocompatibility Complex Antigens too
MHC Class II – at least 6
Structure of MHC I vs. MHC II
MHC I – transmembrane alpha chain (3 domains) + β2-microglobulin
MHC II – heterodimer of 2 transmembrane chains (2 domains each)
MHC variability determines peptide specificity
-
- Cytosolic pathogens
- > degraded in cytosol
- > peptides bing to MHC class I
- > presented to effector CD8 T cells
- > effect on presenting cell - cell death
- Intravesicular pathogens
- > degraded in endocytic vesicle (low pH)
- > peptides bind to MHC class II
- > presented to effector CD4 T cell
- > effect on presenting cell - activation to kill intravesicular bacteria and parasite
- extracellular pathogens and toxins
- > degraded in endocytic vesicle (low pH)
- > peptides bind to MHC class II
- > presented to effector CD4 T cell
- > effect on presenting cell - activation of B cells to secrete Ig to eliminate extracellular bacteria / toxins
MHC class I
Intracellular antigen
Proteasome - antigen processing to peptides in proteasome
peptide transport into endoplasmatic reticulum (ER)
peptide binding by MHC class I
MHC class I present peptide at cell surface
MHC class II
extracellular antigen -> endocytic vesicle
peptide production in phagolysosome
peptide binding by MHC class II
Golgi -> MHC class II in vesicle
MHC class II presents peptide at cell surface
CD8 T-cells + MHC class I
Cytotoxic killer T cells
CTL kill virus infected cell -> apoptotic cell
CD4 T-cells = peptides + MHC class II
TH1 cells:
- > IFN gamma and macrophage containing intracellular bacteria
- > deas intracellular bacteria
TH2 cells:
- > IL 4 / 5/ 13
- > eosinophil, mast cell, plasma cell
TH17 cells:
- > IL 17 -> fibroplasts, epithelial cells + chemokinse
- > neutrophil
TFH cells:
- > B cell with IgM
- > B cell with IgG, plasma cell (isotope switching and affinity maturation)
T reg cells
- > T reg inhibit immature dendritic cell
- > CD4 T cell (lack of T cell activation)
Key facts - Why have 2 types of MHC?
MHC I present Intracellular antigen, e.g viruses.
MHC I - antigen complex recognised by CD8+ve T cells
(T cytotoxic)
CD8+ve T cells kills presenting cell
MHC II present Extracellular antigen, e.g. bacteria
MHC II - antigen complex recognised by CD4+ve T cells
(T helpers)
CD4+ve T cells produce cytokines that promote antibody production (humoral)
Antigen can “swap” & additional T cells recruited
Helper T cell antigen – but now recognisable by Cytotoxic T cell
Cytotoxic T cell antigen – but now recognisable by Helper T cell
Monoclonal Antibodies
An immunological reagent that underpins medicine and is commercially valuable
