The document discusses the major histocompatibility complex (MHC), which plays a key role in the immune system by helping distinguish self from non-self. MHC genes are organized into three classes: class I presents peptides to CD8+ T cells, class II presents peptides to CD4+ T cells, and class III encodes complement proteins and cytokines. MHC molecules contain antigen-binding clefts that present peptide fragments to T cells to initiate immune responses.

1. Phd.dr.sarah
abdulsalam
MAJOR
HISTOCOMPATABILITY
COMPLEX
3rd stage / immunology theory/ lec5

2. Major Histocompatibility Complex(MHC)
 Cluster of genes found in all mammals
 Its products play role in discriminating self/non-self
 Participant in both humoral and cell-mediated immunity
 MHC Act As Antigen Presenting Structures
 In Human MHC Is Found On Chromosome 6, referred
to as HLA complex
 In Mice MHC Is Found On Chromosome 17, referred to
as H-2 complex

3.  Genes Of MHC Organized In 3
Classes:
1. Class I MHC genes
 Glycoproteins expressed on all
nucleated cells
 Major function to present peptide
Ags to CD8 (TC).
2. Class II MHC genes
 Glycoproteins expressed on
Macrophage, B-cells, DCs
 Major function to present
processed Ags peptides to CD4
(TH).
3. Class III MHC genes
 Products that include secreted
proteins that have immune
functions. Ex. Complement system,
inflammatory molecules

4. MHC Molecules
1. Class I MHC Molecule
 Comprised of 2 molecules:  chain and
2-microglobulin
 Non-covalently associated with each
other.
  Chain Made Up Of 3 Domains (1,
2 and 3)
 2-microglobulin Similar To 3
 1 And 2 Form Peptide Binding Cleft
 Interacts with CD8 (TC) molecule .
2. Class II MHC Molecule
 Comprised of  and  chains
  chain and  chain associate non-
covalently
  and  chains Made Up Of
Domains
 1 and 2 ( chain)
 1 and 2 ( chain)
 1and 1 Form Antigen Binding
Cleft
Peptide
binding cleft

5. HLA - Human Leukocyte Antigen
 HLA is the MHC molecules present in human
beings.
 HLA is a set of surface protein present on the
surface of all nucleated cells.
 They are responsible for graft rejection,
adaptive immunity, defense against
infection, some time it is expressed on
cancer cell destruction, certain
autoimmune diseases and certain
complements.
 MHC is the general term referring to the cell
surface antigen of vertebrates.

6. Antigen Processing and presenting
 Extracellular (exogenous) antigens are eliminated by
secreted antibody whereas intracellular (endogenous)
antigens are eliminated by CTLs.
 There are 2 different antigen-presenting pathway to
mediate responses.
- Endocytic pathway
- Cytosolic pathway

7. Cytosolic pathway(endogenous
Ags )
 Endogenous antigens are
degraded into peptides that
can be presented in class I
MHC molecules to TC cells
involving similar mechanisms
as of intracellular proteins.
 Ubiquitin → Ubiquitin-
protein conj → Proteosome

9. Endocytic (exogenous)Pathway
 APCs can internalize antigen by phagocytosis &/or endocytosis.
 Macrophages do both; B cells use receptor-mediated endocytosis.
 After antigen is internalized, it is degraded into peptides.
 The pathway begins by phagocytosis by the cell of a foreign
agent, an organism, bacteria, etc…
 The antigen is now in a phagosome. A lysosome will fuse with
the phagosome to become a phagolysosome.
 The antigen will be degraded into smaller peptides.

10. Endocytic (exogenous)Pathway
 A helper T cell will recognize the complex and trigger
the appropriate response, such as secreting
cytokines and chemokines to control whatever kind
of infection is taking place.
 Internalized antigen takes 1-3 hours to traverse the
endocytic pathway & appear on cell membrane in the
form of peptide-class II MHC complexes.