title: Molecular basis of two novel and related high-prevalence antigens in the Kell blood group system, KUCI and KANT, and their serologic and spatial association with K11 and KETI.
abstract: BACKGROUND
  The numerous antigens in the Kell blood group system result from missense nucleotide changes in KEL. Antibodies to antigens in this system can be clinically important. We describe six probands whose plasma contained antibodies to high-prevalence Kell antigens and discuss their relationship.
  
  
  METHODS
  Polymerase chain reaction amplification, direct sequencing, restriction fragment length polymorphism assays, hemagglutination, flow cytometry, and protein modeling were performed by standard methods.
  
  
  RESULTS
  Proband 1 (KUCI) and her serologically compatible sister were heterozygous for a nucleotide change in Exon 11 (KEL*1271C/T; Ala424Val). Proband 2 (KANT) was heterozygous for KEL*1283G/T (Arg428Leu) and KEL*1216C/T (Arg406Stop) in Exon 11. Red blood cells (RBCs) from Proband 1 and her sister were not agglutinated by plasma from Proband 2; however, RBCs from Proband 2 were agglutinated by plasma from Proband 1. Probands 3, 4, 5, and 6 had the KEL*1391C>T change associated with the previously reported KETI- phenotype. Proband 5 was also homozygous for KEL*905T>C encoding the K11-K17+ phenotype. Hemagglutination studies revealed an association between KUCI, KANT, KETI, and K11. Protein modeling indicated that whereas Ala424 and Arg428 are clustered, Val302 and Thr464 are not.
  
  
  CONCLUSIONS
  Ala424 in the Kell glycoprotein is associated with the high-prevalence Kell antigen, KUCI (ISBT 006032), which is detected by the antibody of Proband 1. Arg428 is associated with the high-prevalence Kell antigen, KANT (ISBT 006033). The association between KUCI, KANT, KETI, and K11 and the results of protein modeling are discussed.
authors.affiliation: Laboratory of Immunohematology and Genomics, New York Blood Center, Long Island City, New York; Laboratory of Immunochemistry, New York Blood Center, New York, New York; Laboratory of Molecular Modeling and Drug Design, New York Blood Center, New York, New York; Laboratory of Membrane Biochemistry, New York Blood Center, New York, New York; Memorial Blood Centers, St Paul, Minnesota; Medcenter One, Bismarck, North Dakota; National Reference Center for Blood Groups, National Institute of Blood Transfusion, Paris, France; Department of Transfusion Medicine, University Hospital Ulm, Institute of Clinical Transfusion Medicine and Immunogenetics, Ulm and German Red Cross Blood Donor Service, Baden-Württemberg-Hessen, Institute Ulm, Ulm, Germany; Laboratory Services Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland; American Red Cross, Southern California Region, Pomona, California.
authors.forename: Randall W
authors.initials: RW
authors.lastname: Velliquette
authors.forename: Kim
authors.initials: K
authors.lastname: Hue-Roye
authors.forename: Christine
authors.initials: C
authors.lastname: Lomas-Francis
authors.forename: Barbara
authors.initials: B
authors.lastname: Gillen
authors.forename: Jennifer
authors.initials: J
authors.lastname: Schierts
authors.forename: Kristie
authors.initials: K
authors.lastname: Gentzkow
authors.forename: Thierry
authors.initials: T
authors.lastname: Peyrard
authors.forename: Inge
authors.initials: I
authors.lastname: von Zabern
authors.forename: Willy A
authors.initials: WA
authors.lastname: Flegel
authors.forename: Karen
authors.initials: K
authors.lastname: Rodberg
authors.forename: Asim K
authors.initials: AK
authors.lastname: Debnath
authors.forename: Soohee
authors.initials: S
authors.lastname: Lee
authors.forename: Marion E
authors.initials: ME
authors.lastname: Reid
mesh_terms: D000328:Adult; D004912:Erythrocytes / Q000276:immunology*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007626:Kell Blood-Group System / Q000235:genetics* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D012698:Serologic Tests; D014018:Tissue Distribution; D065227:Transfusion Reaction
chemical_list: D007626:Kell Blood-Group System
references.citation: Nature. 1996 May 23;381(6580):272
references.pmid: 8692262
references.citation: J Biol Chem. 2001 Jul 20;276(29):27281-9
references.pmid: 11375401
references.citation: Transfusion. 2006 Nov;46(11):1879-85
references.pmid: 17076841
references.citation: J Mol Biol. 1993 Dec 5;234(3):779-815
references.pmid: 8254673
references.citation: Bioinformatics. 2008 Sep 1;24(17):1955-6
references.pmid: 18603567
references.citation: Transfusion. 2009 Apr;49(4):733-9
references.pmid: 19347978
references.citation: Transfusion. 2008 May;48(5):925-9
references.pmid: 18248571
references.citation: Transfusion. 2010 Oct;50(10):2106-16
references.pmid: 20492605
references.citation: Methods Enzymol. 1997;277:396-404
references.pmid: 9379925
references.citation: Blood. 1999 Aug 15;94(4):1440-50
references.pmid: 10438732
references.citation: Vox Sang. 1997;73(1):1-11
references.pmid: 9269063
references.citation: Transfusion. 2007 Jul;47(1 Suppl):32S-9S
references.pmid: 17593284
references.citation: Nucleic Acids Res. 2011 Jan;39(Database issue):D465-74
references.pmid: 21097780
references.citation: Transfusion. 2007 Apr;47(4):703-14
references.pmid: 17381630
references.citation: Transfusion. 2003 Aug;43(8):1121-5
references.pmid: 12869119
references.citation: Immunohematology. 1997;13(3):75-9
references.pmid: 15387772
references.citation: Transfusion. 2006 Aug;46(8):1323-7
references.pmid: 16934067
references.citation: Vox Sang. 2009 Feb;96(2):153-6
references.pmid: 19152607
references.citation: Vox Sang. 2001 Nov;81(4):259-63
references.pmid: 11904003
references.citation: Cell. 1994 Jun 17;77(6):869-80
references.pmid: 8004674
references.citation: Transfus Med Rev. 2000 Apr;14(2):93-103
references.pmid: 10782495
references.citation: Vox Sang. 2011 Jul;101(1):77-82
references.pmid: 21401621
references.citation: Nucleic Acids Res. 2003 Jul 1;31(13):3375-80
references.pmid: 12824331
references.citation: Blood. 1999 Jul 1;94(1):310-8
references.pmid: 10381527
references.citation: J Mol Biol. 2009 Jan 9;385(1):178-87
references.pmid: 18992253
references.citation: Semin Hematol. 2000 Apr;37(2):113-21
references.pmid: 10791880
references.citation: Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6353-7
references.pmid: 1712490
references.citation: Nucleic Acids Res. 2007 Jul;35(Web Server issue):W473-6
references.pmid: 17584791
references.citation: Acta Crystallogr D Biol Crystallogr. 2004 Feb;60(Pt 2):392-6
references.pmid: 14747736
references.citation: Transfusion. 1996 Jun;36(6):490-4
references.pmid: 8669078