Antigens & Antigen Processing Flashcards
What is an immunogen?
An antigen with the ability to stimulate an immune response.
What is a hapten?
An antigen that may bind antibodies, but cannot activate B cells without attachment to another molecule
What is an epitope?
A surface or marker molecule on a larger macromolecule that an antibody binds
What are examples of good immunogens?
Proteins and polysaccharides (B cells only)
Generally speaking, these molecules are poorly immunogenic.
Nucleic acids, lipids
What are T-dependent antigens?
Antigens that require both helper T and B cells to stimulate an antibody response.
What are T-independent antigens?
Non-protein antigens that stimulate an antibody response without assistance from T cells.
What antibody is usually generated in response a T-independent antigen?
IgM
What MHC molecules are recognized by CD8 T cells?
MHC I
What MHC molecules are recognized by CD4 T cells?
MHC II
What are the higly polymorphic MHC I isotypes?
HLA-A, HLA-B, HLA-C
What are the highly polymorphic MHC II isotypes?
HLA-DR
What is the importance of polymorphism in MHC molecules?
Polymorphism allows for the presence of multiple alternative forms of alleles. Polymorphism in MHC allows for diversity in antigen-presenting sites.
What is a haplotype? How does it relate to MHC?
A haplotype is a grouping of genomic variants that tend to be inherited together. MHC genes are inherited as haplotypes. Loci exist for all MHC molecules, but may code for different isotypes.
MHC genes display what type of dominace?
Co-dominance
What cells express MHC I?
All nucleated cells
What cells express MHC II?
Some T cells, B cells, APCs, thymic epithelial cells
Some organisms have mechanisms to prevent expression of MHC in order to prevent immune recognition. How does the immune system respond to cells that do not express MHC I?
If a cell does not express MHC I, it is phagocytized by a NK cell. This process is not antigen-dependent.
How do the structures of MHC I and MHC II differ?
MHC I is made up of three alpha chains and stabilized by a beta 2 monomer. MHC II is a dimer consisting of alpha and beta chains.
How do MHC I and MHC II differ in antigen presentation?
Antigens bind the “floor” of both MHC molecules. MHC I, however, has 2 anchoring domains and thus can only present small fragments of about 8-10 amino acids. MHC II only has one anchoring domain, meaning part of the fragment can extend outside the binding site. This enables MHC II to present longer polypeptide chains of 8-25 amino acids.
What is MHC restriction?
MHC restriction refers to MHC recognition by T cells. T cells can only recognize antigens presented on specific MHC isoforms.
How does MHC bind a T cell?
MHC presents a peptide in the anchoring pocket of the molecule. The peptide is held in place by anchoring residue(s). T cells recognize the polymorphic residues of the MHC molecule that facilitate binding and recognition of the antigen.
What is the difference between exogenous and endogenous peptides?
Exogenous peptides are taken up from the external environment into the cell and are generally presented by MHC II to CD4 T Cells. Endogenous peptides are peptides from within the cell that are presented by MHC I to CD8 T Cells.
Describe the process of exogenous antigen processing and presentation.
Peptides are captured and internalized into endosomes by APCs. The endosome fuses with a lysosome and peptide chains are broken down. MHC II is exported from the ER and fuses with the exocytic vesicle. The peptide-MHC complex is then displayed on the cell surface.
What prevents MHC II from binding with endogenous peptides in the ER before fusion with an exocytic vesicle?
Invariant chains interact with MHC and block the binding groove. Once the vesicle fuses with the endolysosome, proteases act upon the invariant chain to form CLIP. CLIP remains in the peptide binding groove until catalyses remove CLIP so that the peptide can bind.
Describe the process of endogenous antigen processing and presentation.
Some proteins are marked for degradation and transported to proteasomes. The proteasome degrades the protein into peptide fragments. Peptides are transported from the cytosol to the ER by TAP transporter. MHC I loosely binds with TAP, enabling Tapasin to form a bring between MHC I and TAP for the transfer of the peptide into the binding cleft. The MHC-peptide complex is transported to the Golgi for packaging before being expressed on the cell surface for CD8 T Cells.
What types of endogenous proteins would be displayed by MHC I?
Viral gene products, proteins from phagocytosed microbes, mutated/altered host genes
What is cross-presentation?
Describes the ability of dendritic cells to internalize exogenous antigens for expression on either MHC I or MHC II.
