Flashcards in The Major Histocompatibility Complex Deck (20):
What is the MHC?
Family of membrane protein complexes that participate in the immune response, encoded by specific set of genes
Play a role in foreign tissue rejection= Important in differentiating between self and non self
Every nucleated cell of the body has MHC on its membrane
Immune identity + Present peptides to T cells
What do MHC proteins do?
Combine with fragments of antigens that have been digested within the cell
MHC-Antigen complex --> Inserted into cell membrane= Antigen is visible on extracellular surface
Free antigen in ECF cannot bind to unoccupied MHC receptors on cell surface
Vital for presentation of antigen to T cells
What is histocompatibility?
Histo= Tissue compatibility= Skin grafts are a measure of tissue matching
Major and minor
Minor: Some genetic loci were found to influence skin graft acceptance but were not dominant= Some influence on whether or not the material is accepted as self or non self
Example: H-Y= Associates with Y chromosome, only in males
Major: Genetic loci have significant effect= Difference in MHC= Will have the biggest influence on whether or not the material is self or non self
Major= Cluster together in the genome
Man: HLA= Major
What does allogeneic mean?
Grafts from someone with differences at various loci= Graft rejection
Graft= Piece of living tissue that is transplanted
What does syngeneic mean?
If alleles of MHC are matched between individuals, graft is usually accepted
E.g. identical twin
What does autologous mean?
Grafts coming from the individual themselves
What do T cells recognise?
Recognise antigens as peptides= NOT AS PROTEINS
Antigenic peptides have to be presented to T cell receptors by MHC molecules
Function of MHC molecules= Presenting peptides to T cells or else T cells will not 'see' them
T cell receptors have curves corresponding to shape of MHC molecule and peptide= Binds strongly to MHC and peptide combination presented
B cells= Do not need MHC to 'see' antigen
What are class I MHC molecules? What is their structure?
Found in all nucleated human cells, encode class I molecules that are expressed on surfaces of all nucleated cells as 2 polypeptide chains
Viruses or bacteria invade the cells, they are digested into peptide fragments and loaded onto MHC-1 'platforms'
Present peptides derived from intracellular, cytosolic proteins
What is the structure of class I MHC molecules?
Molecule has heavy chain and light chain + 4 globular domains= 3 on heavy chain, 1 on beta2- microglobulin
Light chain: beta-2 micro globulin= Not coded by MHC, not very polymorphic= could be identical in many people
Heavy chain: Is very polymorphic, could be very different between individuals
Member of immunoglobulin supergene family member= 90 amino acids + intrachain disulphide bond
What is some of the features of the peptide binding groove?
The heavy chain= Forms 'binding groove' for peptides
When class I molecule is synthesised, it is able to interact with and bind certain kinds of peptides
Function of H-chain= Binding with peptides non-covalently
B2-microglobulin= Stabilises the molecule and permit it to be displayed on cell surface
Only 1 peptide can bind
Peptide is buried in the molecule
What is Class II MHC?
Found primarily on the antigen presenting cells e.g. macrophages, B lymphocytes, and dendritic cells
Immune cell= Engulfs and digests an antigen= Fragments are returned to the immune cell membrane combined with MHC-II proteins
Helper T cells encounters antigen presenting cell- MHC-II
Result: Helper T cell responds by secreting cytokines= Enhance immune response
Encode structural glycoproteins found on B cells, APC
What is the structure of Class II MHC?
4 globular domains=
2 heavy chains each with 2 globular domains + bound together as transmembrane proteins
Similar to class I structure
Alpha helices form edge of peptide binding grooves
PEPTIDE BINDING IS MUCH LOOSER: Groove is much wider than for Class I and the peptide stretches out more
Both chains form the peptide binding groove + longer and can overhang peptide binding groove
Peptide is longer and can overhang peptide binding groove
What are the loci for MHC Class I genes?
3 types of genes:
What are the loci for MHC Class II genes?
What is the polymorphic property of MHC cells?
MHC shows tremendous variation between individuals
Genetic diversity= Single locus but multiple alleles in population, the more alleles for single locus, the greater the polymorphism
Polymorphism= Genetic variation
Many genes coding for MHC molecules= Many alternative forms of genes for each subregion of MHC
Each MHC locus can encode for a very large number of different allelic forms= 6 different loci
Humans= locks is found on chromosome and encodes HLA (Human Leukocyte Antigens)
Combinations of many different allelic forms which are codiminatly expressed= Chances of 2 individuals having completely identical set of alleles is very small
BASICALLY: Huge number of alleles (variations of genes) which people inherit from parents
What is Polygenic diversity?
Have lots of different copies of genes which fulfil the same role= Generates some diversity
MHC= Polymorphic + Polygenic diversity
Multiple loci (positions of genes) which fulfil the same role, and for every one of loci there are many different alleles present
What is co-dominant?
All alleles for the classes do not get suppressed e.g. the 3 different loci for class I, there are 2 alleles for each (one from mum, one from dad) = Everyone has 6 copies of MHC Class I heavy chain genomes
All 6 gets expressed= 6 possible variants of the heavy chains on cell surface
Number of closely linked genes= Close together
How are the MHC inherited?
Low meiotic recombination= Does not shuffle around as much= Will just be inherited as haplotype
The combination of encoded alleles at each of the loci within the MHC on the same chromosomes
Genes within MHC are closely linked, haplotypes are usually inherited intact
Heterozygous human: Inherits one paternal and one maternal haplotype, each containing 3 Class-I and three class II loci
How does MHC fit into immune system as whole?
Repository for us to be able to identify immune differences
Tend to select mates with different immune system to us