MHC Flashcards
What is the difference between B and T cells, specifically regarding recognition of cognate antigens?
B cells are able to recognize (with antibody Ig on surface) peptides, carbohydrates, lipid, nucleic acids, soluble antigens, particulate T cells can only recognize peptides B cells are typically sampling via IgG, then endocytose entire complex and present ONLY peptides on MHCs
What is the difference in structure between MHC class I and II?
MHC Class I is formed by a single MHC gene encoded alpha chain (1,2,3), and a non MHC gene subunit called beta-2-microglobulin (these are the 2 sets of the heterodimer). Alpha 1 & 2 domains form the peptide binding cleft. Alpha 3 domain is an Ig with a transmembrane region that anchors the complex MHC Class II is formed by an alpha and beta chain heterodimers. Alpha 1 and beta 1 form the peptide binding celft and alpha 2 and beta 2 form the Ig part that has transmembrane regions
How are MHC molecules different in binding compared to T-cells and antibodies?
MHC binding is promiscuous – can bind to many different types of peptides and present them. Unlike T-cells and antibodies that are highly specific to their antigenic determinants.
How do MHC I & II molecules differ regarding binding?
MHC class 1 only binds peptides that are 8-10 amino acids in length. The ends of the binding cleft are closed. There is more stabilization of binding with contact with carboxyterminal and aminoterminal ends. MHC class II has an open binding cleft. Must bind peptides at least 13 AA in length up to 35 AA or even longer (hot dog in a bun).
What are anchor residues for MHC?
These are the specific residues in the peptide binding cleft that determine the MHC general specificity for binding. Both MHC class I and MHC class II molecules have pockets within their binding grooves that accommodate particularly shaped amino acid side chains. The interactions between the binding grooves and these anchor residues are responsible for the bulk of the affinity between the peptide and the MHC molecule
MHC I processes and presents antigens from?
intracellular pathogens
MHC II processes and presents antigens from?
extracellular pathogens
What is TAP-1 and TAP2?
2 proteins of the TAP transporter complex TAP transports peptides from the cytosol into the ER to be placed on MHC class I complexes
Describe how an intracellular pathogen is presented on MHC. in detail from the beginning of the the MHC complex
Bacteria is degraded, or viral proteins are degraded by proteosome. Peptide fragments are transported through the TAP transporter complex and loaded onto MHC Class 1 by the peptide loading complex. The peptide must meet the MHC’s specifics. For a Class 1, 8-10 and Class II, 13+ Here, since it is intracellular pathogen, mostly class I. After being loaded through TAP and peptide loading complex, moves on to Golgi and then the cell membrane
What if there is a genetic deficiency of either TAP-1 or TAP-2 or both?
Would not be able to load peptides onto MHC class 1 molecules in the ER, so would have a decreased antigen presenting response for intracellular pathogens.
What do MHC present?
peptides typically, always presenting peptides, which are typically self peptides but when infection is occurring, will present more MHC loaded with pathogen’s peptides
What is the requirement for MHC on antigen presenting cells to present to naive T-cells?
B7 (on APC) to CD28 on T-cell (what makes APCs different than every other cell) Co-stimulation
What if a MHC peptide that is not on an APC is presented to a naive T-cell? What happens?
Nothing. At least not an immune response
What if any cell presents MHC peptide to an EFFECTOR T-CELL?
The effector T-cell will recognize the cell as infected and effect its destruction
Describe how an extracellular pathogen is presented on MHC. in detail from the beginning of the the MHC complex
Only APCs make and present MHC Class II. MHC Class II complexes are made in the ER but are loaded with an invariant chain that has a piece that sits in the peptide binding cleft of MHC to prevent peptides from binding to it. once the vesicle has budded off the Golgi, the MHC II + Invariant chain is inside the vesicle. The invariant chain is cleaved, leaving only a short peptide in the binding groove called CLIP. When the extracellular bacteria is endocytosed, this is called a phagosome, and it fuses with the vesicle, forming a phagolysosome. When this fusion occurs, HLM-DM knocks CLIP out, allowing degraded peptides from the pathogen bind to the MHC II peptide binding cleft. The loaded MHC Class II complex is now ready to go to the cell membrane to present to naive T cells.
