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A unique major histocompatibility complex Class II–binding register correlates with HLA‐DR11–associated immunogenicity of the major K blood group antigen
Author(s) -
Gunasekera Devi,
Zimring James C.,
Pratt Kathleen P.
Publication year - 2018
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/trf.14525
Subject(s) - immunogenicity , epitope , human leukocyte antigen , antigen , peptide , major histocompatibility complex , biology , avidity , microbiology and biotechnology , immunology , biochemistry
BACKGROUND Kell is a glycoprotein expressed on red blood cells (RBCs). Its K and k variants contain either Met (K antigen) or Thr (k antigen) at Position 193, respectively. Development of anti‐K after K‐mismatched antigen exposure via blood transfusions or pregnancy can destroy RBCs, leading to hemolytic transfusion reactions and hemolytic disease of the fetus and newborn. The immunogenicity of overlapping 15‐mer Kell peptides with M193 or T193 at every possible position was investigated previously. Interestingly, Peptide W179 to M193, with the polymorphic M193T residue at the peptide's C‐terminus, was the most effective at stimulating CD4 T cells from a series of K‐immunized women. STUDY DESIGN AND METHODS This study investigates the basis for HLA restriction of anti‐K immune responses. Major histocompatibility complex Class II (MHCII)‐binding prediction algorithms and quantitative peptide–MHCII‐binding assays were employed to determine the binding registers; anchor residues; and affinities of wild‐type, truncated, and sequence‐modified K and k peptides. Predictions were generated using Immune Epitope Database and ProPred algorithms. Competitive peptide–MHCII‐binding assays utilized 12 recombinant HLA‐DR proteins, K and k peptides, and high‐affinity MHCII‐restricted reference peptides. RESULTS The peptide–MHCII‐binding assays identified a unique K peptide–binding register (W179‐S187) restricted to HLA‐DRB1*11:01, in addition to partially overlapping binding registers that included the K/k M193T polymorphic site and that bound promiscuously to multiple HLA‐DR proteins. CONCLUSION Three partially overlapping MHCII‐binding motifs for HLA‐DRB1*11:01 result in high‐avidity K‐peptide binding, which may contribute to HLA‐DR11‐restricted immunogenicity associated with the K allele.