Extended molecular characterization of HLA genes in the IHWG reference B-lymphoblastoid cell lines (B-LCLs) was one of the major goals for the 17th International HLA and Immunogenetics Workshop (IHIW). Although reference B-LCLs have been examined extensively in previous workshops complete high-resolution typing was not completed for all the classical class I and class II HLA genes. To address this, we conducted a single-blind study where select panels of B-LCL genomic DNA samples were distributed to multiple laboratories for HLA genotyping by next-generation sequencing methods. Identical cell panels comprised of 24 and 346 samples were distributed and typed by at least four laboratories in order to derive accurate consensus HLA genotypes. Overall concordance rates calculated at both 2- and 4-field allele-level resolutions ranged from 90.4% to 100%. Concordance for the class I genes ranged from 91.7 to 100%, whereas concordance for class II genes was variable; the lowest observed at HLA-DRB3 (84.2%). At the maximum allele-resolution 78 B-LCLs were defined as homozygous for all 11 loci. We identified 11 novel exon polymorphisms in the entire cell panel. A comparison of the B-LCLs NGS HLA genotypes with the HLA genotypes catalogued in the IPD-IMGT/HLA Database Cell Repository, revealed an overall allele match at 68.4%. Typing discrepancies between the two datasets were mostly due to the lower-resolution historical typing methods resulting in incomplete HLA genotypes for some samples listed in the IPD-IMGT/HLA Database Cell Repository. Our approach of multiple-laboratory NGS HLA typing of the B-LCLs has provided accurate genotyping data. The data generated by the tremendous collaborative efforts of the 17th IHIW participants is useful for updating the current cell and sequence databases and will be a valuable resource for future studies.

Anthony Nolan Research Institute Royal Free Hospital London UK; UCL Cancer Institute Royal Free Campus London UK

Biomedical Research Foundation Academy of Athens Hellenic Cord Blood Bank Athens Greece

Department for Blood Group Serology and Transfusion Medicine Medical University of Vienna Vienna Austria

Department of Histocompatibility and Immunogenetics NHS Blood and Transplant London UK

Department of Human Genetics McGill University and McGill University and Genome Quèbec Innovation Centre Montreal Canada

Department of Pathological Physiology and Immunogenomics IMTM Faculty of Medicine and Dentistry Palacky University Olomouc Czech Republic

Department of Pathology and Laboratory Medicine Baylor University Medical Center Dallas USA

Department of Pathology and Laboratory Medicine UCLA Immunogenetics Center Los Angeles CA USA

Department of Pathology Stanford University School of Medicine Palo Alto CA USA; Histocompatibility Immunogenetics and Disease Profiling Laboratory Stanford Blood Center Palo Alto CA USA

Department of Pathology University of California San Diego La Jolla CA USA

Fred Hutchinson Cancer Research Center Seattle WA USA

Health Sciences Center Kuwait University Kuwait

Histocompatibility and Immunogenetics Service Development Laboratory NHS Blood and Transplant London UK

Histocompatibility Immunogenetics and Disease Profiling Laboratory Stanford Blood Center Palo Alto CA USA

HLA Department Kashi Clinical Laboratories Inc Portland OR USA

HLA Laboratory American Red Cross Philadelphia PA USA

HLA Laboratory City of Hope Duarte CA USA

HLA Laboratory Division of Haematology McGill University Health Centre Montreal Canada

Immunogenetics Laboratory The Children's Hospital of Philadelphia Philadelphia PA USA

Immunogenetics Laboratory The Children's Hospital of Philadelphia Philadelphia PA USA; Department of Pathology and Lab Medicine University of Pennsylvania Philadelphia PA USA

Immunology Department Hospital Clinic de Barcelona University of Barcelona IDIBAPS Barcelona Spain

Laboratory of Translational Immunology UMC Utrecht Utrecht Netherlands

Molecular Biology Research Department One Lambda Thermo Fisher Scientific Canoga Park CA USA

Stanford Genome Technology Center Palo Alto CA USA

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