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Printable Handouts
Navigable Slide Index
- Introduction
- The MHC and MHC molecules (1)
- What is the MHC?
- A big puzzle for many years
- MHC classical and non-classical molecules (1)
- Classical MHC molecules play central roles in the adaptive immune system (1)
- Two great domains of the cell: the cytoplasm and contiguous structures like the nucleus intracellular vesicles (similar to extracellular space)
- CD8 T cells recognise class I molecules that bind peptides predominantly from the cytoplasm and contiguous structures like the nucleus
- CD4 T cells recognise class II molecules that bind peptides predominantly from intracellular vesicles and the extracellular space
- Classical MHC molecules play central roles in the adaptive immune system (2)
- Classical and some non-classical class I molecules: important roles in immunity and other processes
- T cells sense presence of antigen with positive signal while NK cells sense a balance of positive and negative signals
- Some non-classical class I molecules are recognised by non-conventional T cells
- The MHC and MHC molecules (2)
- Class I and class II molecules look similar but with different domain and gene organisations
- A more detailed structure of a classical class I molecule
- Class I and class II molecules have similar domain structures, but differ in many details
- Peptides bound to class I molecules have a few anchor residues which bind into deep(er) pockets
- Peptides bound to class I molecules are tied down at the ends and bulge in the middle
- In contrast, peptides bound to class II molecules lie flat and hang out the ends, with multiple anchor residues
- TCRs generally bind a diagonal footprint on top: CDR1 and CDR2 over the MHC, and CDR3 over the peptide
- TCRs generally bind a diagonal footprint on top, while co-receptors CD4 and CD8 focus (mostly) on a loop
- Human NKRs (KIRs) bind the two alpha-helices on the top, along with a bit of the peptide
- The MHC and MHC molecules (3)
- MHC classical and non-classical molecules (2)
- Typically, there are few classical MHC molecules, but there can be many non-classical MHC-like molecules
- In mouse and humans, there are many non-classical class I-like molecules with a range of functions (1)
- In mouse and humans, there are many non-classical class I-like molecules with a range of functions (2)
- In mouse and humans, there are many non-classical class I-like molecules with a range of functions (3)
- In mouse and humans, there are only three non-classical class II molecules
- The MHC and MHC molecules (4)
- The human MHC is an enormous region with many genes and much recombination separated into three big regions
- MHC organisation is similar (but not identical among placental mammals
- Summary
Topics Covered
- The definition and the central role of MHC molecules
- Classical class I and class II MHC molecules
- Non-classical MHC molecules
- MHC genes and organization in humans and mice
- Differences between class I and class II molecules
- The function of different MHC molecules in human and mice
Links
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Talk Citation
Kaufman, J. (2022, May 8). The MHC and MHC molecules 1 [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 15, 2024, from https://doi.org/10.69645/SZFW8916.Export Citation (RIS)
Publication History
Financial Disclosures
- There are no commerical/financial matters to disclose.
The MHC and MHC molecules 1
Published on May 8, 2022
42 min
Other Talks in the Series: The Immune System - Key Concepts and Questions
Transcript
Please wait while the transcript is being prepared...
0:00
Hello.
This is Jim Kaufman
from the University of Edinburgh
and the University of Cambridge,
with the first of two talks
on the MHC and MHC molecules.
0:12
We're going to cover a variety
of topics in these two talks.
But we're going to begin
this first talk with
the definition and the central
role of MHC molecules.
0:24
First, what is the MHC?
It stands for the major
histocompatibility complex.
It was discovered
first in mice as
a histocompatibility
two, or H-2, locus
and then in humans as HLA,
or Human Leukocyte Antigen.
These two genetic loci
were the loci that were
most responsible for
rapid graft rejection.
That's reflected in the name.
It's the major complex or region
that's responsible for the
compatibility of tissues,
which is what 'histo' means.
We now know that both of these
regions are really large
and they determine the
"transplantation antigens"
for which there are thousands
of genetic variants,
which geneticists
call "alleles".
These are the molecules
or genes that are matched
by "tissue typing"
for transplants
in order to avoid rejection
by the immune system.
H-2 and HLA are the best
characterized mammalian MHCs,
due to their importance
in biomedicine.
1:31
It was a big puzzle
for many years
as to why this complicated
system evolved.
It has many thousands
of MHC alleles
and involves robust
immune responses
and it seemed ridiculous
that it existed
just to frustrate
transplant surgeons.
Now we know that MHC
molecules are used by
the immune system to detect
infections inside cells,
cancers and threats
outside of cells.
The high polymorphism,
that is the large
number of alleles,
is (mostly) driven by a molecular
arms race with pathogens.