The MHC complex is a cluster of genes present in all mammals that plays an important role in self/non-self discrimination. MHC genes code for cell surface antigens that present antigens to T cells and are highly polymorphic between individuals. There are four classes of MHC molecules: Class I presents endogenous antigens to CD8+ T cells on all nucleated cells; Class II presents exogenous antigens to CD4+ T cells on antigen presenting cells; Class III proteins have immune functions; Class IV is no longer used. The MHC complex is crucial for immune recognition and response.

2. MHC COMPLEX
•The MHC complex is a tightly- linked cluster of genes present in all
mammalian species. The products (proteins) of these genes play an
important role on intercellular recognition, ag presentation and
discrimination between self and non-self by inducing both HI and CMI.
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8. •MHC genes code for cell surface histocompatibility antigens are so polymorphic
that virtually no two human beings have the same set of HLA antigens.
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10. • The rejection of transplanted graft tissue between genetically non-identical individuals is
brought about by the MHC antigens. Hence, the MHC molecules are also called as
transplantation antigens.
• MHC molecules are classified into four classes, namely
• Class I MHC molecules
• Class II MHC molecules
• Class III MHC molecules and
• Class IV MHC molecules.
Class I and Class II MHC molecules belong to the immunoglobulin super family.
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GENE
ARRANGE
MENT

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ß2 microglobulin is located on a different chromosome (15).
GENE
ARRANGE
MENT

13. GENES OF MHC ORGANIZED IN 3 CLASSES
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• CLASS I MHC GENES
• Glycoproteins found on all nucleated cells except RBCs. They present
processed endogenous ag to Tc cells.
• CLASS II MHC GENES
• Glycoproteins found on APC – dendritic cells, macrophages, B cells
and other cells. They present exogenous ag to TH cells.
• CLASS III MHC GENES
• Products that include secreted proteins that have immune functions.
Eg. Complement system, inflammatory molecules- cytokines and heat
shock proteins.

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15. ANTIGEN PROCESSING AND AG PRESENTATION
Proteins present inside the cells are periodically broken down into short peptide fragments by
appropriate enzyme mechanism (Ag processing).
These peptide fragments are displayed as peptide antigens by MHC molecules on the surface of the
cell (Ag Presentation) .
MHC molecules display both self peptides derived from their own proteins and foreign peptides
derived from invading pathogens if any.
The IS constantly watch the surface of the cells for peptides presented by MHC and identifies the
self ag and the foreign ag that are dangerous.
The IS also monitors the amount of MHC presented ags, which helps to target and destroy cancer
cells that often display increased amounts of self ags.
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16. •Among the 4 MHC classes, Class I and Class II MHC molecules are worked in ag
presentation.
•MHC molecules always recognize only T lymphocytes.
•Class I MHC molecules are recognized by CD8+ receptor of cytotoxic T cells (Tc).
•Class II MHC molecules recognize CD4+ receptor of helper T cells (Th).
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17. Structure of class I MHC molecule
• Class I MHC molecules consist of 2 poly peptide chains namely 𝛂-
chain and ß2 microglobulin.
• 𝛂- chain is encoded by the BCA region of HLA and ß2 is encoded
elsewhere.
• The MHC encoded pp is about 350 AAs long with total mol. Wt. of 45
Da. This PP folds into three separate globular domains called 𝛂1,
𝛂𝟐 𝐚𝐧𝐝
𝛂𝟑 𝐰𝐢𝐭𝐡 𝐭𝐫𝐚𝐧𝐬𝐦𝐞𝐦𝐛𝐫𝐚𝐧𝐞 𝐠𝐥𝐲𝐜𝐨𝐩𝐫𝐨𝐭𝐞𝐢𝐧 𝐚𝐧𝐝 𝐜𝐲𝐭𝐨𝐩𝐥𝐚𝐬𝐦𝐢𝐜 𝐭𝐚𝐢𝐥.
• ß2 microglobulin is a 12 kDa PP that is non-covalently associated
with the 𝛂𝟑 domain.
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18. Structure of class I MHC molecule
•There are 4 regions in MHC I:
•Peptide binding region- a groove formed from ∝1 and ∝2
domains of the chain.
•Immunoglobulin like region- highly conserved ∝3 domain,
a site to which CD8 on Tc cell binds.
•Transmembrane region- stretch of hydrophobic amino
acids spanning membrane.
•Cytoplasmic region – sites for phosphorylation and binding
to cytoskeletal elements.
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19. FUNCTION OF CLASS I MHC OR ENDOGENOUS PATHWAY
• Class I MHC molecules present endogenous ags on the
surface of all nucleated cells.
• They present peptides derived from cytosolic proteins.
• So, the pathway of class I MHC presentation of ags is
often called as cytosolic or endogenous pathway.
• It can also present peptides generated from exogenous
proteins through cross presentation.
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21. CLASS I
MHC/ENDO
GENOUS
PATH WAY
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22. STRUCTURE OF CLASS II MHC MOLECULE
• Class II MHC molecules are found only on a few specialized cell
types, including macrophages, dendritic cells and B cells, of all
which are professional ag- presenting cells (APCs).
• It binds with the exogenous (endocytic degradation) antigens.
• It binds with CD4+ adhesion molecules of TH cells.
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23. STRUCTURE OF CLASS II MHC MOLECULE
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24. CLASS II
MHC/EXO
GENOUS
PATH WAY
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28. Cross presentation
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29. ROLE OF CROSS PRESENTATION
• Cross presentation is necessary for immunity against tumors.
• It is necessary for immunity against viruses that do not infect APCs. Eg. Herpes virus, Influenza
virus.
• It is required for the induction of cell mediated immunity by vaccination. Eg. Tumor vaccines.
• It avoids viral immune evasion strategies such as suppression of antigen processing.
• It provides immune defense against bacteria. Eg. Mycobacterium tuberculosis, E. Coli.
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all

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33. FUNCTIONS OF MHC
• Induce the differentiation and maturation of T cell to form functional T cell repertoire.
• Present ag to initiate immune response with a phenomena known as MHC restriction.
• Endogenous ag is presented to CD8+ of Tc cell by MHC class I molecule.
• Exogenous ag is presented to CD4+ of TH cell b MHC class II molecule.
• Participant in both humoral and cell-mediated immunity.
• Discriminate self and non-self ags.
• They mediate autoimmune diseases.
• They bring about graft rejection.
• They provide defense against infections and diseases.
• Paternity testing.
• They are responsible for individual smell of people.
• Important in determining the compatibility of tissues in successful grafting between donor and recipient.
• Anthropology to study races and nations.
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34. MCQ
1. T cells recognise antigen
a) In a 3 dimensional form
b) In solution in the plasma
c) When presented on the surface of antigen presenting cells
d) Following presentation by pattern recognition receptors
2. Major histocompatibility complex is a tight cluster of linked___________
a) carbohydrates
b) proteins
c) genes
d) lipid molecules
3. What is the name of mhc in humans?
A) HLA
b) H2
c) adjuvants
d) haplotype
4. Which of the following polypeptide is important for the expression of MHC I on the
cell membrane?
a) Interferons
b) β2-microglobin
c) Lymphokines
d) Interleukins
5. Which of these are non-professional antigen presenting cells?
a) macrophages
b) dendritic cells
c) fibroblast
d) B lymphocytes
6. Name the cell which receives antigen presented by MHC molecule.
a) NK cells
b) B-cells
c) T-cells
d) Macrophages
7. Name the class of MHC which is recognized by CD4 TH cell.
a) MHC cannot recognize T cells
b) MHC III
c) MHC I
d) MHC II
8. Which MHC molecule recognizes CD8 TC cells?
a) MHC I
b) MHC II
c) MHC III
d) HLA-C
ANSWERS: 1 C, 2 C , 3 A, 4 b, 5 c 6 c, 7 d, 8 a
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