A new strategy for systematically classifying HLA alleles into serological specificities

HLA, vol. 100, pp. 193–231

Abstract

HLA serological specificities were defined by the reactivity of HLA molecules with sets of sera and monoclonal antibodies. Many recently identified alleles defined by molecular typing lack their serotype assignment. We surveyed the literature describing the correlation of the reactivity of serologic reagents with AA residues. 20 - 25 AA residues determining epitopes (DEP) that correlated with 82 WHO serologic specificities were identified for HLA class I loci. Thirteen DEP each located in the beta-1 domains that correlated with 24 WHO serologic specificities were identified for HLA-DRB1 and -DQB1 loci. The designation of possible HLA-DPB1, -DQA1, -DPA1, and additional serological specificities that result from epitopes defined by residues located at both -DQA1 and -DQB1 subunits were also examined. HATS software was developed for automated serotype assignments to HLA alleles in one of the three hierarchical matching criteria: (1) all DEP (FULL); (2) selected DEP specific to each serological specificity (SEROTYPE); (3) one AA mismatch with one or more SEROTYPES (INCOMPLETE). Results were validated by evaluating the alleles whose serotypes do not correspond to the first field of the allele name listed in the HLA dictionary. Additional 85 and 21 DEP patterns that do not correspond to any WHO serologic specificities for common HLA class I and DRB1 alleles were identified, respectively. A comprehensive antibody identification panel would allow for accurate unacceptable antigen listing and compatibility predictions in solid organ transplantation. We propose that antibody-screening panels should include all serologic specificities identified in this study.

Authors 8

1. Kazutoyo Osoegawa corresponding

   Stanford Blood Center

   Affiliation as printed

   Histocompatibility and Immunogenetics Laboratory Stanford Blood Center Palo Alto California USA

   Histocompatibility and Immunogenetics Laboratory Stanford Blood Center Palo Alto California USA

2. Steven G. E. Marsh

   Anthony Nolan · The Royal Free Hospital · University College London

   Affiliation as printed

   Anthony Nolan Research Institute & UCL Cancer Institute, Royal Free Campus London UK

   Anthony Nolan Research Institute & UCL Cancer Institute, Royal Free Campus, London, United Kingdom

3. Rhonda F. Holdsworth

   Australian Red Cross Lifeblood

   Affiliation as printed

   Australian Red Cross Lifeblood Melbourne Victoria Australia

   Australian Red Cross Lifeblood Melbourne Victoria Australia

4. Sebastiaan Heidt Aachen Department of Immunology Leiden University Medical Center Leiden The Netherlands Department of Immunology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Immunology Leiden University Medical Center Leiden The Netherlands

   Department of Immunology, Leiden University Medical Center, Leiden, the Netherlands

5. Gottfried Fischer

   Medical University of Vienna

   Affiliation as printed

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

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

6. Cathi L. Murphey
   Affiliation as printed

   Histocompatibility and Immunogenetics Laboratory at Southwest Immunodiagnostics, Inc. San Antonio Texas USA

   Histocompatibility and Immunogenetics Laboratory at Southwest Immunodiagnostics, Inc. San Antonio Texas USA

7. Martin J. Maiers

   National Marrow Donor Program

   Affiliation as printed

   Center for International Blood and Marrow Transplant Research Minneapolis Minnesota USA

   Innovation National Marrow Donor Program Minneapolis Minnesota USA

   Innovation National Marrow Donor Program Minneapolis Minnesota USA

8. Marcelo Fernández-Viña corresponding

   Stanford Blood Center · Stanford Medicine · Stanford University

   Affiliation as printed

   Department of Pathology Stanford University School of Medicine Palo Alto California USA

   Histocompatibility and Immunogenetics Laboratory Stanford Blood Center Palo Alto California USA

   Department of Pathology Stanford University School of Medicine Palo Alto California USA

   Histocompatibility and Immunogenetics Laboratory Stanford Blood Center Palo Alto California USA