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    Major Histocompatibility Complex

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    nikita
    The major histocompatibility complex (MHC) is a collection of genes on chromosome 6 that encode three classes of molecules. Class I MHC genes encode glycoproteins that present peptides to T cytotoxic cells. Class II MHC genes encode glycoproteins expressed on antigen-presenting cells that present peptides to T helper cells. Class III MHC genes encode various secreted proteins involved in immune functions like the complement system and inflammation.

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    Major Histocompatibility Complex

    Uploaded by

    nikita
    77 views16 pages
    The major histocompatibility complex (MHC) is a collection of genes on chromosome 6 that encode three classes of molecules. Class I MHC genes encode glycoproteins that present peptides to T cytotoxic cells. Class II MHC genes encode glycoproteins expressed on antigen-presenting cells that present peptides to T helper cells. Class III MHC genes encode various secreted proteins involved in immune functions like the complement system and inflammation.

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    The major histocompatibility complex (MHC) is a collection of genes on chromosome 6 that encode three classes of molecules. Class I MHC genes encode glycoproteins that present peptides to T cytotoxic cells. Class II MHC genes encode glycoproteins expressed on antigen-presenting cells that present peptides to T helper cells. Class III MHC genes encode various secreted proteins involved in immune functions like the complement system and inflammation.

    Copyright:

    © All Rights Reserved
    Download as PPTX, PDF, TXT or read online from Scribd
    Download as pptx, pdf, or txt
    77 views16 pages

    Major Histocompatibility Complex

    Uploaded by

    nikita
    The major histocompatibility complex (MHC) is a collection of genes on chromosome 6 that encode three classes of molecules. Class I MHC genes encode glycoproteins that present peptides to T cytotoxic cells. Class II MHC genes encode glycoproteins expressed on antigen-presenting cells that present peptides to T helper cells. Class III MHC genes encode various secreted proteins involved in immune functions like the complement system and inflammation.

    Copyright:

    © All Rights Reserved
    Download as PPTX, PDF, TXT or read online from Scribd
    Download as pptx, pdf, or txt
    of 16

    Major Histocompatibility Complex

    Dr. Devinder Toor


    Major histocompatibility complex
    • is a collection of genes arrayed within a long continuous
    stretch of DNA on chromosome 6 in humans
    • MHC is referred to as the HLA complex in humans.
    • MHC genes - organized into regions encoding 3 classes of
    molecules
    • Class I MHC genes
    • encode glycoproteins expressed on the surface of
    nearly all nucleated cells
    • Major function of the class I gene products is
    presentation of peptide antigens to TC cells.
    • Class II MHC genes
    • encode glycoproteins expressed primarily on antigen-
    presenting cells (macrophages, dendritic cells, and B
    cells)
    • where they present processed antigenic peptides to
    TH cells.
    • Class III MHC genes encode
    • various secreted proteins that have immune
    functions
    • including components of complement system &
    molecules involved in inflammation.
    • Class I & class II MHC mols have common structural features
    and both have roles in Ag processing and presentation.

    • In contrast, class III MHC region, which is flanked by class I & II


    regions, encodes molecules that are critical to immune
    function but have little in common with class I or II molecules.
    • Class III products include
    – Complement components - C4, C2, BF
    – Inflammatory cytokines – TNF & HSP.
    Class I Molecules
    • Class I MHC molecules - contain a 45 kDa chain associated
    noncovalently with a 12-kDa β2-microglobulin molecule.
    • β2-Microglobulin - protein encoded by a highly conserved gene
    located on a different chromosome.
    • Association of α chain with β2-microglobulin - required for
    expression of class I mols on cell membranes.
    • The chain is anchored in plasma membrane by its hydrophobic
    transmembrane segment & hydrophilic cytoplasmic tail.
    • Structural analyses revealed - α chain of class I MHC
    molecules is organized into three external domains (1, 2 & 3),
    each containing approximately 90 amino acids.
    • A transmembrane domain of about 25 hydrophobic aa
    followed by a short stretch of charged (hydrophilic) aa.
    • A cytoplasmic anchor segment of 30 aa.

    • β2-microglobulin is similar in size & organization to α3 domain


    • Does not contain a transmembrane region & is noncovalently
    bound to the class I glycoprotein.
    • The α1 & α2 domains interact to form a platform. The
    structure forms a deep groove, or cleft.
    • Peptide-binding cleft is located on top surface of class I MHC
    molecule
    • Large enough to bind a peptide of 8–10 aa.
    • The α3 domain appears to be highly conserved among class I
    MHC mols & contains a sequence that interacts with CD8
    membrane molecule present on TC cells.
    • β2-Microglobulin interacts extensively with α3 domain & also with
    amino acids of the α1 & α2 domains.
    • Interaction of β2-microglobulin & a peptide with class I chain is
    essential for class I molecule to reach its fully folded conformation.
    • Assembly of class I molecules is believed to occur by the initial
    interaction of β2-microglobulin with the folding class I chain.
    • In the absence of 2-microglobulin, the class I MHC chain is not
    expressed on the cell membrane.
    • This is illustrated by Daudi tumor cells, which are unable to
    synthesize β2-microglobulin.
    Class II Molecule
    • Class II MHC molecules contain two different polypeptide
    chains, a α 33-kDa chain & a β 28-kDa chain, which associate
    by noncovalent interactions
    • Like class Iα chains, class II MHC molecules are membrane-
    bound glycoproteins that contain external domains, a
    transmembrane segment & a cytoplasmic anchor segment.
    • Each chain in a class II molecule contains two external
    domains: α1 & α2 domains in one chain and β1 & β2 domains
    in the other.
    • The membrane-distal portion of a class II molecule is
    composed of the 1α & 1β domains and forms Ag binding cleft
    for processed Ag.
    Class III
    • Class III region of MHC in humans contains a heterogeneous
    collection of genes.
    • These genes encode several complement components, two
    steroid 21-hydroxylases, two heat-shock proteins & two
    cytokines (TNF- and TNF-).
    • Some of these class III MHC gene products play a role in
    certain diseases. For example, mutations in genes encoding
    21-hydroxylase have been linked to congenital adrenal
    hyperplasia.
    • Unlike class I & II MHC molecules, class III molecules are not
    membrane proteins & are not related structurally to class I
    and II molecules, and have no role in Ag presentation,
    although most play some role in immune responses.

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