The first Kell system antibody was described in 1946, shortly after the implementation of the use of the then recently described rabbit anti-human globulin reagent. The system's clinical importance was obvious from the first case: an example of hemolytic disease of the newborn. As with most systems, over the years, more antigens have been found that were proven by inheritance to be of the Kell blood group system. At present it is a system comprised of 22 blood group antigens, several having been shown to be products of allelic genes. Some of the antigens have also shown a distinct racial prevalence (K antigen is more frequently found in Northern European, the Jsa antigen is most frequently found in those of African descent and the Kpc antigen has been more frequently found in Japanese). All of this was very suggestive of a chromosome location that might have three or more regions with mutation points.
The Kell antigens are encoded by a chromosomal location on the long arm of chromosome 7. They are located on a 93 kDa type II glycoprotein that makes a single pass through the membrane, is glycosolated at five sites and functions as a metalloprotease. The Kell antigen appears to be found on erythroid and nonerythroid tissue (primarily in testis). In nonerythroid tissues, as exemplified by skeletal muscle, Kell is disulfide-linked to XK.
This system, as with several other systems, has examples of "depressed phenotypes" and "null phenotypes". The McLeod phenotype (first detected during the investigation of the cells of a Dr. McLeod) have suppression of all inherited Kell blood group antigens, in addition to a unique red blood cell morphology; acanthocytes. Interestingly, the "null phenotype" cells, referred to as Ko, which by definition have no Kell blood group antigens, has normal discocytes.
The expression of the Kell genes is modified by epistatic effects, both from the Kell locus and from at least two regulatory genes, one of which is X-borne (see Kx).