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
What is the reason for hypermutation?
in order to generate populations with the ability to present almost every possible antigen MHC has a high rate of mutation
what species have limited MHC diversity?
cheetahs, tasmanian devils, giant pandas
Why can MHC mols able to present a wide variety of processed peptides?
by having several loci which code for mols of the same fn and by having many alleles within the population.
-Both alleles from each locus can be expressed by the same cell type
What is the heritability of MHC alleles linked to?
Linkage of MHC alleles with specific disease susceptibility traits or autoimmune pathologies
- various alleles can lead to presentation/non-recognition of certain epitopes
- MHC loci are inherited normally, offspring inherit one allele from each parent
The high number alleles assure what?
that most individuals are heterozygous at each of the MHC loci
What do MHC alleles provide?
variation in which particular antigens are presented
-each MHC allele confers recognition of different peptides
What does the variation of MHC alleles result in?
one individual being able to mount an effective immune response to a given pathogen while another (who has a diff allele) presents a different, less important epitope of that pathogen
There are 50-100,000 MHC class I and class II mols on the surface of a typical cell. Most are occupied by what?
normal or self-antigens
Empty MHC molecules are…?
NOT stable on the cell surface
What is the process of Ag presentation and processing?
internalization of Ag into APC –> Ag processing –> generation of multiple peptides, one of which can bind to class II allele –> T cells respond to immunodominant peptide epitope
True or False: a given cell or APC will have many different epitiopes displayed on its surface
True, including self peptpides
A specific immune response will be initiated only if what occurs?
a T cell with the correct receptor encounters that epitope, in the context of MHC molecules
Where are MHC class I mols expressed?
by every nucleated cell
Where are MHC class II mols expressed?
primarily by WBCs
What do the MHC mols influence?
whether or not antigen-specific immune response will occur
-many examples of autoimmunities linked to presence of specific alleles for MHC genes
In animals, what is the MHC linked to?
both immune and production traits
Give some examples
Cattle: blood neutrophil counts, mastitis freq
Sheep/coat: incidence of scrapie
pigs: litter size, ovulation rate, piglet viability, growth performance
equine: risk of recurrent uveitis, sarcoid tumors, insect bite allergies, response to Equine Infectious Anemia Virus
What is MHC restriction?
a given T cell receptor will only recognize Ag presented by a particular(self) MHC mol
-T cells educated in one MHC allele/epitope will not interact with APC unless it expresses that allele bearing that same epitope
