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Printable Handouts
Navigable Slide Index
- Introduction
- The MHC and MHC molecules (1)
- MHC organisation is similar (but not identical) among placental mammals
- Nomenclature for genes
- Nomenclature for alleles
- Nomenclature for haplotypes
- Nomenclature for human HLA haplotypes
- MHC haplotypes exist even in outbred humans
- MHC classical and non-classical molecules
- Historic selection is indicated by dN/dS values
- The MHC and MHC molecules (2)
- The discovery of transplantation antigens
- Mouse genetics is largely based on inbred strains
- A little bit of genetics
- Graft rejection
- Transplantation is of great medical importance
- Transplantation does not explain high MHC polymorphism
- Why have graft rejection (allo-recognition)?
- The MHC and MHC molecules (3)
- The price of a strong response to pathogens is immunopathology, autoimmunity and allergy (1)
- Association of autoimmune diseases, allergies and asthmas with classical MHC alleles
- The strongest associations of autoimmune diseases are by far with the MHC
- Disease associations using dense maps of single nucleotide polymorphisms (SNPs)
- Rheumatoid arthritis has strong associations with MHC and smoking
- Rheumatoid arthritis has strong associations with MHC and smoking (2)
- Rheumatoid arthritis arises because of T cell selection in the thymus
- Ankylosing spondylitis has strong associations with HLA-B27
- Celiac disease (gluten enteropathy) has strong associations with MHC and gluten
- In celiac disease (gluten enteropathy) tTG turns gluten peptides into DQ2 binders
- The price of a strong response to pathogens is immunopathology, autoimmunity and allergy (2)
- The MHC and MHC molecules (4)
- A long history of MHC associated with mate choice and kin recognition
- Interaction between KIR and class I molecules determines placental success (1)
- Interaction between KIR and class I molecules determines placental success (2)
- Reproduction and resistance to infectious disease depend on different KIR:MHC combinations
- The MHC and MHC molecules (5)
- A molecular arms race drives the polymorphism of MHC molecules
- MHC associations with infectious disease are weaker than with autoimmune disease
- AIDS is due to HIV infection
- Disease progression may depend on clonal exhaustion of CTLs
- The MHC is associated with disease progression
- Progression of HIV to AIDS correlates with HLA-B alleles that bind special peptides
- Tapasin-independent alleles confer slow progression to AIDS
- Heterozygous advantage and B*35-Cw04 disadvantage for resistance to AIDS
- Epistatic interaction between KIR3DS1 and HLA-B delays the progression to AIDS
- Cell surface expression of HLA-C correlates with protection
- MHC-determined resistance to HIV progression can be due to multiple mechanisms
- Summary
Topics Covered
- Genetics, nomenclature, polymorphism, and function of MHC molecules
- Mouse genetics is largely based on inbred strains
- Transplantation and T cell selection in the thymus
- Autoimmunity, allergy, and immunopathology
- MHC and mate choice and reproduction
- MHC-determined pathogen and infectious disease resistance
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Talk Citation
Kaufman, J. (2022, May 8). The MHC and MHC molecules 2 [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 22, 2024, from https://doi.org/10.69645/ZZYQ7873.Export Citation (RIS)
Publication History
Financial Disclosures
- There are no commerical/financial matters to disclose.
The MHC and MHC molecules 2
Published on May 8, 2022
51 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 second of
two lectures on the
MHC and MHC molecules.
0:12
In our last talk,
we defined MHC molecules
and discussed their
central role.
We considered the classical class
I and class II MHC molecules
and the non-classical MHC
molecules in some detail
and we finished with the
organisation of MHC genes
in the MHC of humans and mice.
In the second talk,
we're going to consider
more closely genetics,
nomenclature, polymorphism
and function.
Then ask the
question what drives
the high polymorphism of
classical MHC molecules?
0:45
Last time we finished
with this picture
of the human and mouse MHCs,
which are extremely complex
with hundreds of genes,
including those encoding the
classical and non-classical
MHC molecules.
Let's discuss the nomenclature,
particularly of the
classical MHC molecules.
1:05
How are these genes named?
Starting with the
classical class I genes.
For humans, these genes are
called HLA -A, B, and C.
For mouse H-2K, D, and
in some haplotypes, L.
As we mentioned last time,
these genes are due to
different expansions.
HLA-A, B, and C genes
are more closely related
to each other than they are
to any of the mouse genes.
For the classical
class II genes,
there's HLA-DRA and DRB
for the DR α and β gene,
and likewise DQA and
DQB and DPA and DPB.
In mouse, there's H2Eα and Eβ.
But unlike class I genes,
these are direct orthologs
of the human DRA and DRB.
Similarly, H-2Aα and H-2Aβ
are orthologs of DQA and DQB.
But there are no mouse
orthologs of DPA and DPB.
However, there is
a second DRB locus
in most human haplotypes.
The major one is
always called DRB1;
the others have names
like DRB3, DRB5, etc.