Antigen Capture and Presentation Flashcards
What are T cells activated by?
Antigen presenting cells
What do APCs do with antigens?
They capture them in tissues and transport them to peripheral lymphoid tissues where lymphocytes are concentrated to present the antigens to T cells
What are the most common cells to present antigens?
Dendritic cells
Why are co-stimulatory molecules important?
They are another way of regulating responses and are dependent on the pathogen being present so that we don’t develop autoimmunity
What is the role of CB3?
It is involved in signal transduction, not recognition
What types of pathogens does MHC-1 present and to what type of T-cell?
Intracellular pathogens to CD8+ T cells
What types of pathogens does MHC-2 present and to what type of T-cell?
Extracellular pathogens to CD4+ T cells
What is the MHC locus?
A collection of genes found in all mammals that code for MHC molecules
The locus contains two sets of highly polymorphic genes (class I and II)
What is polymorphism?
Multiple alleles of a gene within a population
How does MHC interact with peptides?
Most MHC peptide binding clefts have pockets
Sided chains of 2 or 3 amino acids of antigenic peptides fit into the MHC pockets and anchor the peptide in the MHC peptide-binding cleft
Additional amino acid resides of the antigenic peptide extend upwards and are recognized by TCR
Why do MHC molecules have broad specificity?
Because any given MHC can present any peptide with the correct anchor reside, allowing a small number of MHC molecules to display a large array of peptide antigens
How are MHC-peptide complexes stable?
Peptides remain on display for up to days which maximizes the likelihood of encountering the correct T cell
Which cells express class II MHC?
Dendritic cells, macrophages, B cells
Which cells express class I MHC?
All nucleated cells
What is the structure of class 1 MHC?
An alpha chain noncovalently linked to a beta2-microglobulin chain
What do alpha1 and alpha2 domains form in a class 1 MHC?
A peptide binding groove that holds peptides of 8-11 amino acids
How does the TCR interact with the MHC molecule?
The TCR sits down on top of the MHC molecule and contacts residues extending up and out of the peptide binding groove on the antigenic peptide
Where are polymorphic residues located on class 1 MHC molecules?
in the alpha1 and alpha2 domains
What is the role of the alpha3 domain on class 1 MHC molecules?
It is invariant and contacts only the T cell CD8 co-receptor
Only CD8 T cells respond to class 1 MHC-bound antigens
What is the role of TAP in antigen processing?
TAP binds peptides and transports them from the cytosol into the lumen to bind MHC
What happens if a class I molecule stably blinds a microbial peptide?
The complex is sent to the cell surface via the Golgi and exocytic vesicles
What does the class I pathway respond to?
Intracellular microbes
Where do class I MHC molecules present intracellular microbes?
On the surface of all nucleated cells
What recognizes the class I MHC-peptide complex?
CD8 T-lymphocytes that upon activation will differentiate into cytotoxic T lymphocytes to kill infected cells
What is the structure of class II MHC molecules?
An alpha chain noncovalently linked to a beta chain
What do the alpha1 and beta1 domains on a class II MHC molecule form?
A peptide binding groove that holds peptides of 10-30 amino acids
What residues does the TCR contact from class II MHC molecules?
Residues of the antigenic peptide that extend up out of the peptide binding groove
Where are the polymorphic residues of class II MHC located?
In the alpha1 and beta2 domains
Which domain on class II MHC molecules is invariant?
The beta2 domain that contacts the T cell CD4 co-receptor
Thus, only CD4 T cells respond to class II presented antigens
What does the class II pathway respond to?
Extracellular microbes
What do CD4 T cells stimulate B lymphocytes to do?
Produce antibodies and phagocytes to ingest and destroy microbes
What is the co-dominance of MHC molecules?
Both parental alleles are expressed equally
Each individual can express up to 6 different class I molecules and 10 to 20 different class II molecules
What are the 5 features of peptide binding to MHC?
Each MHC molecule displays 1 peptide at a time
Broad specificity
Very slow off-rate
Stable expression requires peptide
MHC molecules bind only peptides
What is the significance of MHC molecules displaying only one peptide at a time?
Each T cell responds to a single peptide bound to an MHC molecule
What is the significance of broad specificity for peptide binding to MHC?
Many different peptides can bind to the same MHC molecule
What is the significance of a very slow off-rate for peptide binding to MHC?
MHC molecule displays bound peptide for long enough to be located by a T cell
What is the significance of why stable expression requires a peptide for MHC?
Only MHC molecules that are displaying peptides are expressed for recognition by T cells
