The major histocompatibility complex (MHC) plays a key role in the immune system by presenting antigens and distinguishing self from non-self. It is located on chromosome 6 in humans and contains genes like HLA that determine disease susceptibility. MHC molecules come in two classes: class I present intracellular peptides and class II present extracellular peptides. Variants in MHC genes can increase risk for certain diseases, like a variant in HLA-DQ increasing susceptibility to type 1 diabetes. Loss of MHC diversity in some populations like cheetahs can also lead to increased disease emergence due to a less broad range of antigens recognized.

1. MHC AND DISEASE
SUSCEPTIBILITY
PRESENTED BY,
D.IRENE
16PGZ001.
M.Sc. Zoology (spl in Biotechnology),
Lady Doak College,
Madurai.

2. https://en.wikipedia.org/wiki/Jean_Dausset#/media/File:Je
an_Dausset_1968.jpg
Jean Dausset

3. Immune cells recognize
foreign antigens…..??????

5. LOCATION OF MHC
In chromosome 6
In humans it is – HLA complex
In mice it is- H-2 complex

6. MAJOR HISTOCOMPATIBILTY
COMPLEX
Intercellular
recognition
Discrimination of
self and non-self
Involves in humoral
and cell mediated
immune responses
As antigen
presenter
Determines the
response of the
individual to antigens

7. http://nakimedicalblog.tumblr.com/post/67561960318/im
mense-immunology-insight-delayed-type-of

8. Classes of MHC moelcules
Class 1 MHC Class 2 MHC Class 3
MHC

9. Class 1 MHC molecule
-45 kDa α and 12kDa β2
microglobulin.
-α chain is a transmembrane
glycoprotein encoded by
polymorphic genes within the
A, B, and C regions of the
human HLA complex.
-peptide size 8-10 amino acids.

10. Class 2 MHC
molecule
-non identical glycoprotiens .
-33kDa α chain and 28kDa β
chain.
-α1, α2 and β1 and β2 domains
-peptide size 13-18 amino acids.

11. Peptides bound with mhc

12. -Allelic variants of MHC are many.
-codominantly expressed.
-a group of linked MHC genes is generally inherited from
parents. – haplotypes
- Because of individual allelic differences in the peptide binding
clefts of the class I MHC molecules, different
individuals within a species will have the ability to bind
different
sets of viral peptides
-broad specificity.

13. MHC and disease susceptibility
HLA genes occur at a higher frequency-
Diseases associated with MHC-

15. -Even a single amino acid difference in the peptide- binding groove can have a
profound impact on the spectrum of both self and foreign peptides that are
presented. Thus, an aspartic acid at amino acid residue position 57 in the HLA -
DQ β chain confers resistance, whereas an alanine, valine or serine at this
position confers susceptibility, to type 1 diabetes.
-Studies of knockout mice that lack
the gene for β2-microglobulin demonstrate
that MHC class I products on cell
surfaces are necessary for the maintenance
of normal iron metabolism. These
mice, which are unable to express any of
their class I molecules on the cell surfaces,
suffer from iron overload with disease
consequences similar to HH.
https://en.wikipedia.org/wiki/HLA-DQ

16. Disease susceptibility in cheetah
Loss of MHC
diversity – lead to
the emergence of
diseases in cheetah
population.
http://www.slideshare.net/JuliusManolong/cheetah-
genetic-diversity

17. -High level of MHC polymorphism that has been observed in various species may provide
the advantage of a broad range of antigen presenting MHC molecules.
-MHC diversity appears to protect a
species from a wide range of infectious diseases

18. 1. Richard Goldsby, Janis Kuby., Immunology, 5th edition. pg 162-182.
2.Ivan .M Roitt., Roitts essential immunology.,12th edition., pg 482-486.
3.https://www.ncbi.nlm,nih.gov/pmc /articles/PMC248657/
4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291482/
5. http://www.els.net/WileyCDA/ElsArticle/refId-a0024246.html