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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.
- Source :
- Transfusion; May2018, Vol. 58 Issue 5, p1171-1181, 11p, 7 Charts, 1 Graph
- Publication Year :
- 2018
-
Abstract
- <bold>Background: </bold>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.<bold>Study Design and Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusion: </bold>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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00411132
- Volume :
- 58
- Issue :
- 5
- Database :
- Complementary Index
- Journal :
- Transfusion
- Publication Type :
- Academic Journal
- Accession number :
- 129257196
- Full Text :
- https://doi.org/10.1111/trf.14525