Chapter 4: Major histocompatibility complex I and II

Chapter 4: Major histocompatibility complex I and II

About MHC class I and MHC class II:
• The Major histocompatibility (MHC) is a critical portion of the immune system’s ability to discern self from non-self as well as detect when the body’s own cells are either infected or have undergone malignant change.
• There are two major classes of MHC involved in the human immune system; these two classes are both structurally and functionally distinct from one another.

MHC class I 

MHC class I
• MHC class I is present on all nucleated cells in the body
• It is encoded by Human Leukocyte Antigen (HLA) genes: HLA-A, HLA-B, and HLA-C.
• It is a cell surface protein that displays peptide fragments from inside the cell on the outside.
• Functionally, antigen is loaded onto the MHC I in the rough endoplasmic reticulum and transported via Transporter associated with Antigen Processing (TAP) before being inserted into the cell membrane. 
• Normally, the antigen that is loaded onto MHC I is self-antigen, and cytotoxic T cells (CD8+ T cells) will not react to it.
• If a virus infects a cell, however, the virus produces viral proteins using the host’s cellular machinery. These viral proteins will also be loaded onto MHC I.
• This is how cytotoxic T cells confer immunity to viral infection. They recognize MHC I with loaded viral antigen and targets it for cytotoxic destruction if the proper co-stimulatory signal is present. 
• Mnemonic: “Be rough on yourself.”
Self-antigen is loaded on class I in the rough endoplasmic reticulum.

MHC class II

MHC class II
• MHC class II is present only on antigen-presenting cells such as macrophages and dendritic cells.
• It is encoded by Human Leukocyte Antigen genes: HLA-DP, HLA-DQ, and HLA-DR.
• Structurally, it is composed of two a- and two ß-subunits.
• After Antigen Presenting Cells (APCs) phagocytose microbes, they are delivered to endosomes where acid proteases degrade protein antigens.
• Endosomes fuse with lysosomes to form an acidified vesicle. Newly synthesized MHC class II molecules pass through such acidified vesicles and bind peptide fragments of the antigen, transporting the peptides to the cell surface.
 
What prevents MHC II from binding to the cell’s own polypeptides?
• An invariant chain blocks the peptide-binding groove and directs the newly synthesized MHC II molecules to the acidified intracellular vesicles.

• The MHC class II inserted into the cell membrane aids in the binding and recognition of the antigen by TCR (T cell receptor) on helper T cells (CD4+ T cells). Helper T cells can then activate B cells and/or trigger local inflammation.

Various ways of remembering the difference between MHC class I and II:

CD8+ T-cells recognize MHC I:

·        It takes only 1 stroke of the pen to write “8”

·        CD8 x MHC1 = 8

·        CD8+ are Cytotoxic T cells because "EighT" has T for "Toxic"

CD4+ T-cells recognize MHC II:

·        It takes 2 strokes of the pen to write “4”

·        CD4 x MHC2 = 8

·        CD4+ are Helper T cells because “Cells ask for (four, 4) help”

MHC class I:

·        The genes have only one alphabet. (HLA-A, HLA-B, HLA-C)

·        All cells have one nucleus; so all nucleated cells have class I MHC.

·        MHC I has one chain (alpha chain) & one microglobulin (Beta 2 microglobulin).

MHC class II:

·        The genes have two alphabets. (HLA-DP, HLA-DQ, HLA-DR)

·        Present in cells that love to (two) eat (Phagocytes).

·        MHC II has two chains. (One alpha & one beta).

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