Molecular Basis of Kell Blood Group Phenotypes

Abstract

The molecular basis of different Kell blood group phenotypes is reviewed. Sequence analysis of the Kell gene (KEL) established that single base substitutions, resulting in amino acid changes, are responsible for the different phenotypes. Most of the amino acid substitutions, with the exception of the one responsible for expression of KEL6 (Js^a), occur at the amino-terminal half of the protein, a domain that has least amino acid homology with a family of zinc endopeptidases, which include neutral endopeptidase 24.11 and endothelin-converting enzyme-1. Some of the genes were expressed in transfected cells and typed with alloantibodies to confirm that the identified mutations are responsible for antigen expression. Clinical applications of Kell blood group genotyping which include prenatal diagnosis to monitor hemolytic disease of the newborn are discussed.

Expression of C antigen in transduced K562 cells

“…In contrast, six nucleotide differences leading to four amino acid changes are found when sequences encoding C or c antigen are compared: Cys16, Ile60, Leu68, and Ser103 when C is found and Trp, Leu, Asn, and Pro when c is found. 9 The occurrence of structurally independent polymorphic antigens on a single polypeptide is well known in other blood group systems, such as Kell 18 and Lutheran, 19 but the structures of these proteins are very different from the structure of the CE polypeptide. The probable structure of the CE polypeptide suggests that a mutation in one part of the molecule would be likely to influence the structure of the protein at a site that, though distant in terms of the linear sequence, is adjacent in the native folded molecule.…”

“…Oligo d(T [12][13][14][15][16][17][18] ) magnetic beads were used to prepare mRNA according to the manufacturer's instructions (Dynal, Lake Success, NY). Synthesis of cDNA was from 1 µg of mRNA using oligo d(T [12][13][14][15][16][17][18] ) and avian myeloblastosis virus reverse transcriptase (Promega) as described. 4 The cDNA was used as the template for PCR (94°C, 1 min; 60°C, 1 min; 72°C, 2.5 min; 35 cycles) with a sense primer that corresponded to pBabe puro retroviral vector sequence 5´ of the insert site (sense 5´-GCC TCG ATC CTC CCT TTA TCC-3´) and an anti-sense primer to Rh cDNA 3ń oncoding sequence 1327 to 1300 (antisense 5´-TAC AAA TGC AGG CAA CAG TGA GAG GAA G-3´).…”

Onset of expression of the components of the Kell blood group complex

“…1,2 The polymorphism of Kell is due to single-base substitutions that lead to amino acid changes in the coding region. 3 Anti-K (anti-KEL1) can cause fetal anemia by inhibiting the growth of erythroid progenitor cells. 4 Fetal anemia may be due to the immune destruction of erythroid progenitor cells that have reacted with maternal Kell antibodies 5 Although KEL1 is the most immunogenic of all the Kell antigens, other Kell antigens are also immunogens and have been reported to sensitize mothers and cause fetal anemia.…”

The value of DNA analysis for antigens of the Kell and Kx blood group systems

“…Kp b , unlike the other high-prevalence antigens, is associated with two antithetical low-prevalence antigens, Kp a and Kp c . 11 K is the strongest immunogen in the Kell system and is a common cause of antibody production in mismatched transfusions. The KEL1 phenotype is due to a single base mutation, 698C>T (exon 6), which substitutes T193M.…”