ABO Antigens – The Basics Are Important

Overview

The enzymatic process of antigen expression is important to understand because it lays the foundation for understanding ABO type and its implications to clinical and laboratory medicine.

Section Goals

  • Appreciate the diverse nature of red blood cell antigens
  • Understand the process of ABO antigen formation
  • Appreciate the significance of H antigen
  • Name the genes and transferases responsible for expression of the ABO antigens

Red blood cell antigens: a high level view

An antigen is a three dimensional substance on the cell surface that can elicit antibody formation. In transfusion medicine, we focus on antigens on red cells, white cells, or platelets. Antigens can be proteins, glycolipids, or glycoproteins.

Antigen expression is inherited. Individuals can be homozygous for an antigen (inheriting identical alleles from each parent), or heterozygous (inheriting a different allele from each parent).

H antigen

Formation of ABO antigens begins with a basic precursor called H antigen. The H gene, also called FUT1, encodes for the formation of fucosyltransferase, an enzyme that adds fucose onto the precursor chain. Once the fucose is added, we have H antigen.

You need H antigen in order to progress to making A or B antigen. Individuals deficient in the H (FUT1) gene cannot form H antigen and, therefore, cannot form A or B antigen. This is the famous Bombay Phenotype, which we’ll discuss more later.

A antigen

In the formation of blood group A, the A gene (AA or AO) has been inherited. The A gene encodes for N-acetylgalactosaminyltransferase, which adds N-acetyl-D-galactosamine sugar onto the H antigen. This sugar confers A specificity.

B antigen

Blood group B individuals inherit the B gene (BB or BO), which encodes for Galactosyltransferase, which in turn attaches D-galactose to H antigen. This sugar is responsible for B specificity.

AB blood group

AB individuals inherit both both the A and B gene. They have both transferases working and competing with each other to convert H antigen into their respective products. I think it’s important to remember that it is an enzymatic system, thus, there is competition for substrate. This will become important when we learn the implications our blood groups have upon antibody production. Main point for now is to understand that AB individuals have both A antigen and B antigen present on their red blood cells:

O blood group

Group O individuals lack the A and B gene so they lack the transferases that convert H antigen. Therefore, they have a LOT of H antigen on their red blood cells (provided they inherited the H (FUT1) gene, which 99.9% of people do inherit.

Key takeaways:

I know this isn’t the most exciting stuff to learn, but we do have to learn the names of the transferases and their genes. These are easy test questions to get right, and it is important to understand the enzymatic process that results in ABO antigen expression. For now, focus on knowing:

  • H (FUT1) gene encodes for a fucosyltransferase, which makes H antigen.
  • H antigen is a necessary precursor for the formation of A or B antigen.
  • The A gene encodes for N-acetylgalactosaminyltransferase, which makes A antigen by adding N-acetyl-D-galactosamine to H antigen.
  • The B gene encodes for Galactosyltransferase, which makes B antigen by adding D-galactose to H antigen.

Alright! That covers the essential biochemistry we need to know to understand. There are important implications of the ABO groups, which we’ll cover in future lessons.