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H Antigen

H Antigen Structure.001

H antigens are a family of antigens that can perform diverse biological functions for the immune system. These antigens can be classified as either major or minor antigens, depending on whether they present foreign or self-presenting peptides to T cells.

The H gene, located on chromosome 19, codes for the enzyme fucosylytransferase. Once functional, this enzyme is responsible for the addition of a fucose to the terminal sugar of a precursor substance that resides on the surface of red blood cells (RBCs). The biochemical structure of an H antigen consists of a protein with a lipid known as ceramide, and four sugars that extend from the ceramide into the extracellular fluid. In order, going away from the ceramide, these sugars are: galactose, N-acetylgalactosamine, and galactose. The final galactose added to the chain is also attached to a fucose.

Also known as substance H, these antigens become precursors to each of the ABO blood group antigens, which are apparent in all common human blood types, except for those with the Bombay Blood phenotype (see Hh antigen system). If the H antigens are not produced, ABO blood group antigens will not be able to form on those red blood cells.

H antigens are also present in the flagella of motile bacteria. ^[2] The H antigens associated with bacterial flagella function in a similar way to H antigens in other organisms, by enabling the detection of foreign substances and triggering an immune response. ^[2]

Major H Antigens

"Encode molecules that present foreign peptides to T cells".

• Major H antigens are capable of helping the immune system produce antibodies against any foreign substance with the potential to threaten the host organism.
• Includes H-2 and HL-A.

Minor H Antigens

"Present polymorphic self-peptides to T cells".

• Minor H antigens present self-peptides to the T cells, which allows those T cells to recognize the cell is a host cell, and not to target the cell for destruction.
• These are also referred to as the histocompatibility antigen, and are a major factor in graft rejection. Even when Major Histocompatibility Complex genotype is perfectly matched to the graft someone is receiving, minor H antigens can still cause rejection of the graft. ^[1]
• Includes the H-Y antigen.

Relationship to Blood Types

With respect to differentiation between the main blood types (A, B, or O), H antigens are the foundation on which A and B antigens are formed. These "base units" allow for the addition of more antigens, except for blood type O, which does not add any further antigens onto the H antigen. After the H gene has been expressed, either an A or B gene will then be expressed. These genes code for enzymes that will add a specific immunodominant sugar to the H antigen and guarantee specificity within a given blood type.

Blood Type A

This blood type is achieved by the addition of a single galactose onto the previously formed H antigen on the red blood cell. Gene A codes for an enzyme whose function is to place an additional galactose on the end of the sugar chain of the previously formed H antigen. This allows for the blood cells to be distinct from other blood types.

Blood Type B

Similarly to blood type A, type B blood cells are also differentiated by the addition of just one amino sugar derivative of galactose. N-Acetylgalactosamine (GalNAc) is placed on top of the H antigen on the RBCs by an enzyme coded for by gene B, and this is what makes the blood type distinct.

Blood Type O

People with this blood type do not have additional antigens present on the surface of the H antigen. For type O blood to be inherited, the recipient must have two copies of the gene that will be expressed in place of either A or B. In the absence of those genes, an extra antigen will not form and the H antigen (also referred to as the "base unit") will be the only thing expressed on the surface of the RBCs. Of any blood type, type O is the one with the highest presence of H antigen.