5-Major His to Compatibility Complex (MHC)

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    Major HistocompatibilityMajor HistocompatibilityComplex (MHC)Complex (MHC)

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    There are three major histocompatibilityantigens; class I, classII, and class IIIMHC antigens .These antigens are

    genetically determined by a set of genescalled the major histocompatibility genecomplex , which lie on a portion of the shortarm of human chromosome 6.These genesoccupy four regions ( A,B,C and D).

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    HLA (MHC) geneHLA (MHC) gene

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    R egions B,C and A determine the antigenicspecificities of class I MHC surfacemolecules.R egion D determines the antigenic

    specificities of class II MHC surfacemolecules.The region between D and B codes for certain complement components ( C 2,C 4,

    factor B), and is not concerned with graftrejection. It is called class III MHC .

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    Class I MHC antigens: are glycoproteins and

    include HLA-A,HLA-B, and HLA-C . They arefound on all nucleated cells. Class I MHCenables cytotoxic T cells (Tc) to recognizeforeign antigen on the surface of graft cells,

    tumour cells or virus infected cells and kill thesecells. In other words Tc cells ( CD8 )are triggeredonly when they recognize both antigen and classI MHC molecules in close association on the

    surface of cells. This is known as MHC-restriction .

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    Class II MHC-antigens: or HLA-D antigens are

    glycoproteins, and include HLA-DP, HLA-DQand HLA-D R .These are found chiefly on the surface of Tlymphocytes, and antigen presenting cells(APCs) such as monocytes, macrophages,dendritic cells and B lymphocytes.Helper T cells (Th) ( CD4 ) will recognize foreignantigen on the surface of APC only if they areassociated with class II MHC molecules (MHCrestriction ).

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    HLA (MHC)HLA (MHC)

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    Class - I MHC Class - II MHC1- They include classical 1- They include classical

    HLA- A ,B , C HLA- DP ,DQ , D Rnon classical non classical

    HLA- G , E HLA - DM, DO2 - F ound on all nucleated cells 2 -F ound on certain cells

    e.g. T - cells,and APCs.

    3 -Presents the Ag to Tc 3 -Presents the Ag to Th

    4 -Determined by serologic tests 4 -Determined by cellular testse.g. Microcytotoxicity tests e.g. Mixed lymphocyte reaction

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    Both classes could be typed by:ELISA , F low cytometry or molecular

    techniques such as PC R .

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    Importance of MHCImportance of MHC

    1 .Organ transplantation and graft rejection.2.MHC restriction :

    a) Tc cells recognize the Ag in associationwith MHC I.b) Th cells recognize the Ag in association

    with MHC II.

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    3.Disease association : It is found that thepresence of certain HLA antigens is oftenassociated with a particular disease;

    - HLA- B27 with ankylosing spondylitis.- B8 with myasthenia gravis.-DR2 with multiple sclerosis.-DR4 with rheumatoid arthritis

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    4.Paternity testing and forensicinvestigations

    ( An individual inherits one maternal andone paternal chromosome 6).