The Kell antigen system (also known as the Kell–Cellano system) is a
human blood group system, that is, a group of
antigen
In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response.
...
s on the human red blood cell surface which are important determinants of
blood type
A blood type (also known as a blood group) is based on the presence and absence of antibody, antibodies and Heredity, inherited antigenic substances on the surface of red blood cells (RBCs). These antigens may be proteins, carbohydrates, glycop ...
and are targets for
autoimmune
In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an " autoimmune disease" ...
or
alloimmune
Alloimmunity (sometimes called isoimmunity) is an immune response to nonself antigens from members of the same species, which are called alloantigens or isoantigens. Two major types of alloantigens are blood group antigens and histocompatibility a ...
diseases which destroy red blood cells. The Kell antigens are K, k, Kp
a, Kp
b, Js
a and Js
b.
The Kell antigens are
peptides
Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Dalton (unit), Da or more are called proteins. Chains of fewer t ...
found within the Kell protein, a 93-
kilodalton
The dalton or unified atomic mass unit (symbols: Da or u, respectively) is a unit of mass defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at rest. It is a non-SI unit accepted f ...
transmembrane
A transmembrane protein is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequently u ...
zinc
Zinc is a chemical element; it has symbol Zn and atomic number 30. It is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodic tabl ...
-dependent
endopeptidase
Endopeptidase or endoproteinase are proteolytic peptidases that break peptide bonds of nonterminal amino acids (i.e. within the molecule), in contrast to exopeptidases, which break peptide bonds from end-pieces of terminal amino acids. For this r ...
which is responsible for cleaving
endothelin-3.
Protein
The ''KEL'' gene encodes a type II transmembrane
glycoprotein
Glycoproteins are proteins which contain oligosaccharide (sugar) chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known a ...
that is the highly
polymorphic Kell blood group antigen. The Kell glycoprotein links via a single
disulfide bond
In chemistry, a disulfide (or disulphide in British English) is a compound containing a functional group or the anion. The linkage is also called an SS-bond or sometimes a disulfide bridge and usually derived from two thiol groups.
In inor ...
to the
XK membrane protein that carries the
Kx antigen. The encoded protein contains sequence and structural similarity to members of the
neprilysin
Neprilysin (; also known as membrane metallo-endopeptidase (MME), neutral endopeptidase (NEP), cluster of differentiation 10 (CD10) and common acute lymphoblastic leukemia antigen (CALLA)) is an enzyme that in humans is encoded by the ''MME'' ge ...
(M13) family of
zinc
Zinc is a chemical element; it has symbol Zn and atomic number 30. It is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodic tabl ...
endopeptidase
Endopeptidase or endoproteinase are proteolytic peptidases that break peptide bonds of nonterminal amino acids (i.e. within the molecule), in contrast to exopeptidases, which break peptide bonds from end-pieces of terminal amino acids. For this r ...
s.
There are several
allele
An allele is a variant of the sequence of nucleotides at a particular location, or Locus (genetics), locus, on a DNA molecule.
Alleles can differ at a single position through Single-nucleotide polymorphism, single nucleotide polymorphisms (SNP), ...
s of the
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
which creates Kell protein. Two such alleles, ''K
1'' (Kell) and ''K
2'' (Cellano), are the most common. The kell protein is tightly bound to a second protein,
XK, by a
disulfide bond
In chemistry, a disulfide (or disulphide in British English) is a compound containing a functional group or the anion. The linkage is also called an SS-bond or sometimes a disulfide bridge and usually derived from two thiol groups.
In inor ...
. Absence of the XK protein (such as through
genetic deletion
In genetics, a deletion (also called gene deletion, deficiency, or deletion mutation) (sign: Δ) is a mutation (a genetic aberration) in which a part of a chromosome or a sequence of DNA is left out during DNA replication. Any number of nucleoti ...
or through a single point mutation within the coding region of the XK gene), leads to marked reduction of the Kell antigens on the red blood cell surface. Absence of the Kell protein (K
0), however, does not affect the XK protein.
The Kell protein has also recently been designated CD238 (
cluster of differentiation
The cluster of differentiation (also known as cluster of designation or classification determinant and often abbreviated as CD) is a protocol used for the identification and investigation of cell surface molecules providing targets for immunophe ...
238).
Disease association

Kell antigens are important in
transfusion medicine
Transfusion medicine (or transfusiology) is the branch of medicine that encompasses all aspects of the Blood transfusion, transfusion of blood and blood components including aspects related to hemovigilance. It includes issues of blood donation, im ...
,
autoimmune hemolytic anemia
Autoimmune hemolytic anemia (AIHA) occurs when a person's immune system produces antibodies directed against their own red blood cells (RBCs). These antibodies attach to red cells, causing them to break down ( lyse), and reducing the number of ox ...
and
hemolytic disease of the newborn (anti-Kell). Anti-K is the next most common immune red cell antibody after those in the ABO and Rh system. Anti-K typically presents as IgG class alloantibody. Individuals lacking a specific Kell antigen may develop
antibodies
An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that caus ...
against Kell antigens when transfused with blood containing that antigen. This is particularly true for the "K" antigen which shows a relatively high antigenicity and moderately low frequency (~9%) in Caucasian populations. Anti-K can also occur following transplacental hemorrhage associated with childbirth making Kell an important concern for
hemolytic disease of the newborn
Hemolytic disease of the newborn, also known as hemolytic disease of the fetus and newborn, HDN, HDFN, or erythroblastosis fetalis, is an alloimmune condition that develops in a fetus at or around birth, when the IgG molecules (one of the five ...
. Following the formation of anti-K, subsequent blood transfusions may be marked by destruction of the new cells by these antibodies, a process known as
hemolysis
Hemolysis or haemolysis (), also known by #Nomenclature, several other names, is the rupturing (lysis) of red blood cells (erythrocytes) and the release of their contents (cytoplasm) into surrounding fluid (e.g. blood plasma). Hemolysis may ...
. Anti-K does not bind complement, therefore hemolysis is extravascular. Individuals without K antigens(K
0) who have formed an antibody to a K antigen, must be transfused with blood from donors who are also K
0 to prevent hemolysis.
Autoimmune hemolytic anemia
Autoimmune hemolytic anemia (AIHA) occurs when a person's immune system produces antibodies directed against their own red blood cells (RBCs). These antibodies attach to red cells, causing them to break down ( lyse), and reducing the number of ox ...
(AIHA) occurs when the body produces an antibody against a blood group antigen on its own red blood cells. The antibodies lead to destruction of the red blood cells with resulting
anemia
Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availabl ...
. Similarly, a pregnant woman may develop antibodies against fetal red blood cells, resulting in destruction, anemia, and
hydrops fetalis
Hydrops fetalis or hydrops foetalis is a condition in the fetus characterized by an accumulation of fluid, or edema, in at least two fetal compartments. By comparison, hydrops allantois or hydrops amnion is an accumulation of excessive fluid in ...
in a process known as
hemolytic disease of the newborn
Hemolytic disease of the newborn, also known as hemolytic disease of the fetus and newborn, HDN, HDFN, or erythroblastosis fetalis, is an alloimmune condition that develops in a fetus at or around birth, when the IgG molecules (one of the five ...
(HDN). Both AIHA and HDN may be severe when caused by anti-Kell antibodies,
as they are the most immunogenic antigens after those of the
ABO
The ABO blood group system is used to denote the presence of one, both, or neither of the A and B antigens on erythrocytes (red blood cells). For human blood transfusions, it is the most important of the 47 different blood type (or group) cla ...
and
Rhesus blood group system
The Rh blood group system is a human blood group system. It contains proteins on the surface of red blood cells. After the ABO blood group system, it is most likely to be involved in transfusion reactions. The Rh blood group system consisted o ...
s.
McLeod phenotype
McLeod phenotype (or McLeod syndrome) is an
X-linked
Sex linkage describes the sex-specific patterns of inheritance and expression when a gene is present on a sex chromosome (allosome) rather than a non-sex chromosome ( autosome). Genes situated on the X-chromosome are thus termed X-linked, and ...
anomaly of the Kell blood group system in which Kell antigens are poorly detected by laboratory tests. The McLeod gene encodes the XK protein, a protein with structural characteristics of a membrane transport protein but of unknown function. The XK appears to be required for proper synthesis or presentation of the Kell antigens on the red blood cell surface.
History
The Kell group was named after the first patient described with antibodies to K
1, a pregnant woman named Mrs. Kellacher in 1945. Mrs. Cellano was likewise a pregnant woman with the first described antibodies to K
2. The K
0 phenotype
In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology (physical form and structure), its developmental processes, its biochemical and physiological propert ...
was first described in 1957 and the McLeod phenotype was found in Hugh McLeod, a
Harvard
Harvard University is a private Ivy League research university in Cambridge, Massachusetts, United States. Founded in 1636 and named for its first benefactor, the Puritan clergyman John Harvard, it is the oldest institution of higher lear ...
dental student, in 1961.
King
Henry VIII of England
Henry VIII (28 June 149128 January 1547) was King of England from 22 April 1509 until his death in 1547. Henry is known for his Wives of Henry VIII, six marriages and his efforts to have his first marriage (to Catherine of Aragon) annulled. ...
may have had Kell-positive blood type, explaining the deaths of seven of his ten children at, or soon after, birth, supported by the revelation that Henry may have inherited Kell from his maternal great-grandmother,
Jacquetta of Luxembourg
Jacquetta of Luxembourg (1415/1416 – 30 May 1472) was a prominent figure in the Wars of the Roses. Through her short-lived first marriage to the Duke of Bedford, brother of King Henry V, she was firmly allied to the House of Lancaster. Howe ...
. Alternatively he may have had McLeod syndrome, explaining his mental deterioration around age 40.
Other associations
Evidence supports a genetic link between the Kell blood group (on
chromosome 7
Chromosome 7 is one of the 23 pairs of chromosomes in humans, who normally have two copies of this chromosome. Chromosome 7 spans about 160 million base pairs (the building material of DNA) and represents between 5 and 5.5 percent of the total DN ...
q33) and the ability to taste
phenylthiocarbamide
Phenylthiocarbamide (PTC), also known as phenylthiourea (PTU), is an organosulfur thiourea containing a phenyl ring.
It has the unusual property that it either tastes very bitter or is virtually tasteless, depending on the genetic makeup of ...
, or PTC, a bitter-tasting
thiourea
Thiourea () is an organosulfur compound with the formula and the structure . It is structurally similar to urea (), with the oxygen atom replaced by sulfur atom (as implied by the '' thio-'' prefix). The properties of urea and thiourea differ s ...
compound.
Bitter taste receptor proteins in the taste buds of the tongue that recognise PTC are encoded on nearby chromosome
locus 7 q35-6.
References
External links
* - OMIM entry for Kell protein
* - OMIM entry for XK protein
Kellat
BGMUT
The BGMUT (Blood Group antigen gene MUTation) Database documents allele, allelic variations in the genes encoding for human blood group systems. It was set up in 1999 through an initiative of the Human Genome Variation Society (HGVS). Since 2006, i ...
Blood Group Antigen Gene Mutation Database at
NCBI
The National Center for Biotechnology Information (NCBI) is part of the National Library of Medicine (NLM), a branch of the National Institutes of Health (NIH). It is approved and funded by the government of the United States. The NCBI is loca ...
,
NIH
*
{{transfusion medicine
Clusters of differentiation
Blood antigen systems
Transfusion medicine