Wtj. Morgan et Wm. Watkins, Unravelling the biochemical basis of blood group ABO and Lewis antigenic specificity, GLYCOCON J, 17(7-9), 2000, pp. 501-530
The ABO blood-group polymorphism is still the most clinically important sys
tem in blood transfusion practice. The groups were discovered in 1900 and t
he genes at the ABO locus were cloned nearly a century later in 1990. To en
able this goal to be reached intensive studies were carried out in the inte
rvening years on the serology, genetics, inheritance and biochemistry of th
e antigens belonging to this system. This article describes biochemical gen
etic investigations on ABO and the related Lewis antigens starting from the
time in the 1940s when serological and classical genetical studies had est
ablished the immunological basis and mode of inheritance of the antigens bu
t practically nothing was known about their chemical structure. Essential s
teps were the definition of H as the product of a genetic system Hh indepen
dent of ABO, and the establishment of the precursor-product relationship of
H to A and B antigens. Indirect methods gave first indications that the sp
ecificity of antigens resided in carbohydrate and revealed the immunodomina
nt sugars in the antigenic structures. Subsequently chemical fragmentation
procedures enabled the complete determinant structures to be established. D
egradation experiments with glycosidases revealed how loss of one specifici
ty by the removal of a single sugar unit exposed a new specificity and sugg
ested that biosynthesis proceeded by a reversal of this process whereby the
oligosaccharide structures were built up by the sequential addition of sug
ar units. Hence, the primary blood-group gene products were predicted to be
glycosyltransferase enzymes that added the last sugar to complete the dete
rminant structures. Identification of these enzymes gave new genetic marker
s and eventually purification of the blood-group A-gene encoded N-acetylgal
actosaminyltransferase gave a probe for cloning the ABO locus. Blood-group
ABO genotyping by DNA methods has now become a practical possibility.