Molekul pengenal antigen

a. Molekul reseptor antigen

b. Struktur molekul MHC Kelas I dan II
 Preliminary concepts
• Cell receptors or markers confer specificity and
identity
• Major functions of receptors are
1. to perceive & attach to nonself or foreign
molecules
2. to promote the recognition of self molecules
3. to receive & transmit chemical messages among
other cells of the system
4. to aid in cellular development.

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 How are receptors formed?
• As a cell matures, certain genes that encode cell
receptors are transcribed & translated into protein
products with a distinctive shape, specificity and
function.
• Receptor is modified & packaged by the endoplasmic
reticulum & Golgi complex.
• It is ultimately inserted into the cell membrane,
accessible to antigens, other cells, and chemical
mediators.

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Major Histocompatibility Complex (MHC)
• Receptors found on all cells except RBCs
• Also known as human leukocyte antigen (HLA)
• Plays a role in recognition of self by the
immune system and in rejection of foreign
tissue
• Genes for MHC are located on chromosome 6,
clustered in a multigene complex of classes I,
II, III

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MHC receptors

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 Functions of MHC
• Class I – markers that display unique
characteristics of self molecules & regulation of
immune reactions
– Required for T lymphocytes
• Class II – receptors that recognize & react with
foreign antigens. Located primarily on
macrophages & B cells
– Involved in presenting antigen to T cells
• Class III – secreted complement components,
C2 and C4
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 Clonal selection theory
• Lymphocytes use 500 genes to produce a
tremendous variety of specific receptors
• Undifferentiated lymphocytes undergo genetic
mutations & recombinations while they
proliferate in the embryo forming a billion
different clones with the ability to react with a
tremendous variety of antigens.

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• Lymphocyte specificity is preprogrammed,
existing in the genetic makeup before an antigen
has ever entered the system.
• Each genetically different type of lymphocyte
expresses a single specificity.
• First introduction of each type of antigen into the
immune system selects a genetically distinct
lymphocyte and causes it to expand into a clone
of cells that can react to that antigen.
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 Specific B cell receptor:
Immunoglobulin
• Large glycoproteins that serve as specific
receptors of B cells
• Composed of 4 polypeptide chains
– 2 identical heavy chains
– 2 identical light chains
• Y shaped
• Variable regions
• Constant regions

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 Immunoglobulins
• Immunoglobulin genes lie on 3 different
chromosomes
• Undifferentiated lymphocyte has 150 different genes
for the variable region of light chains & 250 for the
variable region and diversity region of the heavy
chain
• During development, recombination causes only the
selected V and D genes to be active in the mature
cell.

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 B cell receptors
• Once synthesized, immunoglobulin is
transported to cell membrane & inserted
there to act as a receptor
• First receptor on most B cells is a small form of
IgM & mature B cells carry IgD receptors

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 T cell receptors
• Formed by genetic recombination, having
variable and constant regions
• 2 parallel polypeptide chains
• Small, without humoral functions

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T cell receptors

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Humoral and cellular immunity
(antibody mediated or cellular)
 Self and nonself
• Markers
– glycoprotein
– located on the cell surface
– Eg. Major histocompatibility complex (MHC)

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 Markers
• Host cells receptors (ex. MHC) confer
specificity and identity
• Role – detection, recognition, and
communication
• Lymphocyte cells recognize the host cell
receptors as “self”
• Lymphocyte cells recognize microbe receptors
as ‘nonself’

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 Major histocompatibility complex (MHC)

• Self receptor
• Glycoprotein
• Found on all nucleated cells
• In humans – Human leukocyte antigen (HLA) is
equivalent to the MHC
• Classes of MHC

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 Classes of MHC
• Each individual has a unique MHC profile
– Expression of a particular combination of MHC
genes
• Class I – all nucleated cells
• Class II – macrophages, dendritic cells, B cells

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The Class I and II MHC for humans are surface receptors
consisting of glycoproteins.

Fig. 15.2 The human major histocompatibility complex. 25

• Class I MHC molecules, found on almost all nucleated
cells of the body
– Display peptide antigens to cytotoxic T cells
Infected cell
1 A fragment of
foreign protein
Antigen (antigen) inside the
fragment cell associates with
an MHC molecule
and is transported
1 to the cell surface.
Class I MHC
molecule
2 2 The combination of
T cell MHC molecule and
receptor antigen is recognized
by a T cell, alerting it
to the infection.

(a) Cytotoxic T cell

• Class II MHC molecules, located mainly on
dendritic cells, macrophages, and B cells
– Display antigens to helper T cells
Microbe Antigen-
presenting
1 A fragment of cell
foreign protein
(antigen) inside the Antigen
cell associates with fragment
an MHC molecule
and is transported
to the cell surface. 1
Class II MHC
molecule
2 The combination of 2
T cell
MHC molecule and receptor
antigen is recognized
by a T cell, alerting it
to the infection.

Helper T cell
(b)
 B cells
Surface bound antibody
Antibody secreting B cell

Antigen

B-cell

Soluble antibodies, circculate in the body

 Antibody secreting B cell

B-cell

Virus killed
 T cells
• Two types:
– Helper T cells (Th): activates other cells
– Cytotoxic T cells (Tc): can kill other cells
• T cells can only recognize antigens
associated with certain molecules (MHC)
Presentation of antigens to T cells
• Proteins (peptides) from inside the cell are
presented by MHC I molecules to Tc cells.
• Proteins (peptides) from the outside of cells
are presented by MHC II molecules to Th
cells.
• MHC I on almost all cells
• MHC II on specialized antigen-presenting cells
 Antigen presentig cell

MHC II + peptide
Th

Virus infected cell, cancer cell

Tc MHC I + peptide
 MHC molecules
• Important to study what parts of a protein
that binds to MHC molecules.
• MHC I binds peptides with 8-10 aa
• MHC II bind peptides with 12-25 aa
• Potentials of peptide vaccines
• Prediction of peptides is important!!!!