slides on MHC

1. MHC
GROUP MEMBERS
 M.Mughees
 Anam Munir
 Iqra Mahyuddin
 Jamshaid Ali
 Irum Arshad
MAJOR HISTOCOMPATIBILITY COMPLEX

2. Major Histocompatibility Complex
Cluster of genes found in all mammals.
It is a set of cell surface proteins essential for the
acquired immune system to recognize foreign molecules
in vertebrates, which in turn determines
histocompatibility.
Involved in
• cell-cell interaction
• antigen presentation
• recognition of self-nonself molecules
• Participant in both humoral and cell- mediated
immunity

3. • In Human, MHC Is Found On Chromosome 6
• Referred to as HLA complex HLA genes are
very diverse (polymorphic) i.e. there are many
alleles of the class I and II genes
• In Mice, MHC Is Found On Chromosome 17
• Referred to as H-2 complex
Class I MHC
• almost all nucleated cells
• antigen presentation to cytotoxic T cells
• Found In Regions A, B and C In Humans (K
and D In Mice)

4. Class II MHC
• on antigen-presenting cells
• antigen presentation to helper T cells
• Found In Regions DR, DP and DQ (IA and IE In
Mice)
• These molecules are cell-surface glycoproteins
• class I and Class II MHC Share Structural Features
• Both involved in APC

5. Class III- MHC
• secreted proteins
( Products that include secreted proteins that have
immune functions.)
• complement components (specifically Bf, C2, and C4)
• Inflammation
• Class III MHC Have No Structural Similarity To
Class I and II

6. CLASS I MHC MOLECULE
• Identified by cytotoxic T cells
• a chain noncovalently attached to b2-microglobulin
• association required for expression of class I
molecules on the cell surface
• Peptide-binding cleft located on top of the surface
of Class I – between a1 and a2
• a chain is a trans membrane glycoprotein
a chain
• a1, a2, a3 – on outside of membrane
• trans membrane domain
• cytoplasmic tail

7. b2-microglobulin
• similar to a3
• no trans membrane region

8. GENE ARRANGMENT
• Total no . Of class I loci varies
• In humans about 20
• In mice 30, but all these are not functional
• In humans the functional loci are A,B,C.
• In mice K,D
• Others are pseudo genes that cannot be
expressed.

9. MHC
• Between the class I and class II gene loci,
there is a third locus (Class III)
• This locus contains genes encoding tumor
necrosis factor, lymphotoxin and two
complement components (C2 and C4)
• Class III antigens do not participate in MHC
restriction or graft rejection.

10. • Class I MHC antigens are : HLA-A, HLA-B and
HLA-C
• These antigens are glycoproteins found on
surfaces of all nucleotide human cells and on
platelets
• HLA-A contains 24 different antigenic
specificities, HLA-B contains 52 and HLA-C
contains 11
Class I MHC antigens are involved of MHC
restriction of cell mediated cytotoxicity
MHC CLASS 1 antigens

11. MHC RESTRICTION
• Endogenously processed cytosolic peptides in
virus infected cells or tumor cells are transported
to the surface of the cells
• They bind to MHC I molecules to be recognized
by cytotoxic T-cells which then kill these cells
• In other words; T-cells are only activated when
they recognize both antigen and class I MHC
molecules in association

13. CLASS II MHC MOLECULE
• Recognized by helper T cells
• HLA-DR
• Structure
 External domains,
 trans membrane segment
 cytoplasmic anchor
• 4 exterior domains – a1, a2, b1, b2
Class II antigens
• Class 2 antigens are: HLA-DP, HLA-DQ, HLA-DR
antigens.

14. • T cellsHLA-DP contain 6 different
antigenic specificities,
• HLA-DQ contains 9 and HLA-DR contains
20
• These antigens are glycoproteins found
on the surface of macrophages, B-cells,
Dentritic cells, langerhans cells of skin
and activated
• Helper T-cells recognize antigens on antigen-
presenting cells only when the antigens are
presented on the surface of cells in
association with class II MHC

15. • Class II antigens react with the CD4 molecule
on the helper T-cells which secrete cytokines

17. CLINICAL IMPORTANCE
• both class I and class II molecules can induce a
response that leads to graft rejection
• (Transplant rejection occurs when
transplanted tissue is rejected by the
recipient's immune system, which destroys the
transplanted tissue).
• MHC antigens also appear to play a role in
development of auto diseases.
• both class I and class II molecules play a
major role in antigen presentation

18. CONTINUED
• They essentially determine the types of peptides
to which an individual can mount an immune
response.
• Although the MHC molecules typically have a
broad binding capacity, small biochemical
differences in these proteins are responsible for
differences seen in the ability to react to a
specific antigen
• . Thus individual’s MHC type for numerous
reasons must be known.

20. • For e.g. hepatitis B
• Do not have the genetic capacity to respond.
But, presence of a particular MHC protein
may confer additional protection.
• vaccines containing certain amino acid
sequences that serve as immunodominant
epitopes can be specifically developed.
• This might avoid the risk associated with
using live organisms.
CONTINUED

21. • Additionally, if an individual suffers from
allergies, knowing a person’s MHC type may
predict the types of allergens
CONTINUED