Molekul pengenal antigen

a. Molekul reseptor antigenb. Struktur molekul MHC Kelas I dan II

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Preliminary concepts

• Cell receptors or markers confer specificity and identity

• Major functions of receptors are1. to perceive & attach to nonself or foreign

molecules2. to promote the recognition of self molecules3. to receive & transmit chemical messages among

other cells of the system4. 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

Humoral and cellular immunity (antibody mediated or cellular)

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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.

Infected cell

Antigenfragment

Class I MHCmolecule

T cellreceptor

(a) Cytotoxic T cell

A fragment offoreign protein(antigen) inside thecell associates withan MHC moleculeand is transportedto the cell surface.

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The combination ofMHC molecule andantigen is recognizedby a T cell, alerting itto the infection.

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2

• Class I MHC molecules, found on almost all nucleated cells of the body– Display peptide antigens to cytotoxic T cells

• Class II MHC molecules, located mainly on dendritic cells, macrophages, and B cells– Display antigens to helper T cells

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Microbe Antigen-presentingcell

Antigenfragment

Class II MHCmolecule

T cellreceptor

Helper T cell

A fragment offoreign protein(antigen) inside thecell associates withan MHC moleculeand is transportedto the cell surface.

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The combination ofMHC molecule andantigen is recognizedby a T cell, alerting itto the infection.

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(b)

B cells

B-cell

Antigen

Antibody secreting B cell

Soluble antibodies, circculate in the body

Surface bound antibody

B-cell

Antibody secreting 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

Th

Tc

Virus infected cell, cancer cell

Antigen presentig cell

MHC II + peptide

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!!!!