Lecture 4 - MHC and Antigen Presentation Flashcards
What is the MHC?
system of gene products used for specifically recognizing and eliminating foreign antigens
- fns to recognize a wide variety of epitopes
- Ags can be from within host cels (endo) or extracellular source (exo)
- both self and non-self antigens are constitutively processed and presented
Define polygenic (MHC)
several genes exist for a given MHC class
Define polymorphic (MHC)
large number of alleles exist for a given gene
Define promiscuous (MHC)
will bind a range of similar epitopes
What are the three regions of the MHC genes?
Class I - single chain, presents endo Ag to CD8+ T cells (cytotoxic T cells)
Class II - 2 chains, presents exo Ag to CD4+ T cells (helper T cell)
Class III - cytokines, heat shock proteins, Ag processing and transport proteins, and complement proteins
Do all vertebrates possess MHC genes?
yes, but number of genes within each class varies -many pseudogenes also exist within locus
Do all classes of MHC have similar fns?
no, Class I and II physically present the Ag on the surface of a cell. Class III is for all other genes in the MHC region.
Describe the structure of MHC Class I
constitutively expressed on surface of all nucleated cells
-single chain non-covalently associated with B2-microglobulin
What is the function of MHC Class I?
presentation of endogenously produced Ag to MHC-restricted, CD8+ T cells.
-This signals cytotoxic T cells to destroy host cells which display abnormal Ag
What is Class I important for?
recognition of virus-infected cells -viral proteins are produced within the host cell and are displayed on the surface in context with MHC class I
Describe the structure of MHC class II
expressed predominantly on immunocytes (WBCs)
-2 polymorphic chains (alpha and beta) that fold together to form a binding pocket for processed antigens
What is MHC promiscuousness
MHC binding pocket is much more flexible than the Ab or TCR binding pocket. There are many peptides that fit, requiring only conservation of the “anchor residues” that interact with the antigen contact residues within the MHC binding pocket
What is the function of MHC class II?
presentation of exogenously produced Ag to MHC-restricted CD4+ T cells
-This activates T helper cells for the purpose of inducing the immune respones, including antibody production, macrophage activation and cytokine cascades
What fits into the binding pocket formed by the MHC chains?
processed antigens –> depending on chemical make up and size
-binding pockets have broad specificity –> many fragments will fit
What is a MHC ARS Hypermutation site?
MHC has a high rate of mutation (many alleles) in the peptide binding cleft
-this changes the specificity btw alleles as to the exact structure that will fit into the cleft