topic 3 Flashcards
What do both types of T cells recognize?
CD8+ T cell-MHC I molecules in dendritic cell, CD4+ T cell-MHC II molecules in macrophages.
How does T cell antigen recognition work?
Protein taken in APC and is broken down. Pieces of protein bind to MHC inside cell and is then present on the cell membrane. The T cell receptor recognizes the protein/MHC complex and binds to it.
What do the different T cells (CD8T, CD4Th1, CD4Th2) bind to?
CD8T binds to virus infected cell and kills it
CD4Th1 binds to a macrophage and releases cytokines to activate it.
CD4Th2 binds to a B cell and releases cytokines to help it produce more antibodies as a plasma cell.
What are the steps in the journey and maturation of dendritic cells?
Dendritic cell (called langerhans in epidermis) binds the antigen using TLRs=TNF and IL-1 from macrophages make the DC less adhesive so it starts moving out of tissue=on its way to LN, microbial binding, T cell chemokines, and TNF and IL-1 from macrophages all increase MHCs and costimulator B7 on the DC surface making it mature (ready to be recognized by t cells).
What are the professional APCs? Which cells do they activate? What is the ultimate result?
Dendritic Cell-Activates naive T-Cell=>clonal expansion and differentiation into effector t cells
macrophage-activates effector t-cell=>activation of macrophages (cell-mediated immunity)
B Cell-activates effector T-cell=b cell activation and antibody production (humoral)
What is the MHC Gene Structure?
Human MHC locus is called the HLA (Human Leukocyte Region).
Class II MHC Locus has DP, DQ, DR
Class I MHC locus has B, C, A
What are the HLA products of HLA genes?
Class 2 regions, DP, DQ, and DR, all encode an alpha and beta subunit, both with variance, which dimerize on the cell membrane.
Class 1 regions, A, B, and C encode an alpha subunit with variance and a Beta 2 M subunit without variance that dimerize.
Variabilty in MHC molecules
There are many different alleles in the population, They are polymorphic genes.
Each individual inherits HLA-A, B, and C from mom and dad (6) and and HLA-DP, DQ, and DR from mom and dad (6).
They vary from person to person and one person’s MHC molecules will bind different peptides than another person’s.
Why is HLA Typing important and how is it done today?
Important for transplants and such. If there aren’t similar HLA types in two individuals, a transplant will be rejected.
Molecular assays are what is used today.
Basic properties of Class I MHC
Recognized by CD8+ T cells (cytolytic)
Alpha chain with two variant domains, and a non variant domain. Beta 2 m is a non variant chain.
Variance occurs at peptide binding groove.
Non-variant alpha domain is a CD8 binding site (CD4 won’t bind there)
Peptides are shorter b/c they can’t hang out of groove.
Occur in all nucleated cells.
Basic properties of Class 2 MHC
Recognized by CD4 T cells (helper)
Two chains, an alpha and beta, each with one variable domain at the peptide binding groove.
The non-variant domain on the beta chain has a CD4 binding site.
Peptides can be longer b/c they’re able to hang out of groove.
Occur only in APCs.
What are the steps in MHC II antigen processing
The antigen is endocytosed from EC into a vesicle which meets with a lysosome—>phagolysosome
The MHC is formed in the ER with an invariant chain and is sent off in a vesicle. The invariant chain is clipped but a peptide, or a clip, is left in peptide binding groove so no peptides can be bound there.
The MHC vesicle binds with phagolysosome at which point clip is removed so a peptide from the antigen can bind. The MHC/Antigen vesicle binds to the cellular membrane and MHC is deposited there.
What are the steps in MHC I Antigen processing
A cytosolic protein (antigen) is chopped up by a proteasome.
The peptides enter the ER via TAP.
The class I MHCs are on the ER membrane.
The peptides bind to the MHCs in the groove and the MHCs go from ER to membrane through golgi and in a vesicle.
General features of peptide binding to MHC
Broad specificity-Many different peptides to same MHC
Each MHC dispays one peptide at a time
MHC molecules only bind peptides
Peptides are acquired during intracellular assembly
Only MHC molecules with peptide end up on surface
There is a very slow dissociation rate
1% of foreign Ag displayed is enough to activate T cell (doesn’t take much).
TCRs recognize both the MHC and the protein and CD8 or CD4 molecules recognize that invariant domain. Associative recognition occurs b/c the protein comes out of the groove in class II MHCs.
What is Cross-presentation
Sometimes a target cell can’t reach LNs and thus T cells, but when they die, they are taken up by APCs and then taken to T-cells.
