The neutrophil alloantigen HNA-3a (5b) is located on choline transporter-like protein 2 and appears to be encoded by an R>Q154 amino acid substitution. Blood 2010 Mar 11;115(10):2073-6
Date
12/31/2009Pubmed ID
20040764Pubmed Central ID
PMC2837332DOI
10.1182/blood-2009-11-248336Scopus ID
2-s2.0-77950438788 (requires institutional sign-in at Scopus site) 84 CitationsAbstract
The molecular basis of the HNA-3a/b (5b/a) leukocyte antigen system has not yet been defined despite evidence that HNA-3a-specific antibodies are particularly prone to cause severe, often fatal, transfusion-related lung injury. We used genome-wide single nucleotide polymorphism scanning and sequencing of DNA from persons of different HNA-3a/b phenotypes to identify a single single nucleotide polymorphism in exon 7 of the CLT2 gene (SLC44A2) that predicts an amino acid substitution in the first extracellular loop of choline transporter-like protein 2, a member of the choline transporter-like protein family of membrane glycoproteins, and correlates perfectly with HNA-3a/b phenotypes (R154 encodes HNA-3a; Q154 encodes HNA-3b). Mass spectrometric analysis of proteins immunoprecipitated from leukocytes by anti-HNA-3a provided direct evidence that anti-HNA-3a recognizes choline transporter-like protein 2. These findings will enable large-scale genotyping for HNA-3a/b to identify blood donors at risk to have HNA-3a-specific antibodies and should facilitate development of practical methods to detect such antibodies and prevent transfusion-related lung injury.
Author List
Curtis BR, Cox NJ, Sullivan MJ, Konkashbaev A, Bowens K, Hansen K, Aster RHAuthor
Brian Curtis PhD Director in the Platelet & Neutrophil Immunology Laboratory department at BloodCenter of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceAmino Acid Substitution
Arginine
Base Sequence
DNA Mutational Analysis
Genome-Wide Association Study
Glutamic Acid
Humans
Isoantigens
Mass Spectrometry
Membrane Glycoproteins
Membrane Transport Proteins
Molecular Sequence Data
Mutant Proteins
Neutrophils
Polymorphism, Single Nucleotide