A new strategy for systematically classifying HLA alleles into serological specificities

Kazutoyo Osoegawa*, Steven G.E. Marsh, Rhonda Holdsworth, Sebastiaan Heidt, Gottfried Fischer, Cathi Murphey, Martin Maiers, Marcelo A. Fernández Viňa*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

9 Citations (Scopus)
58 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)193-231
Number of pages39
JournalHLA
Volume100
Issue number3
DOIs
Publication statusPublished - Sept 2022
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Fingerprint

Dive into the research topics of 'A new strategy for systematically classifying HLA alleles into serological specificities'. Together they form a unique fingerprint.

Cite this