Hematopoietic stem cell transplantation: Improving alloreactive Bw4 donor selection by genotyping codon 86 of KIR3DL1/S1.

Abstract

KIR3DL1 is a natural killer (NK) cell receptor that recognizes the Bw4 epitope of human leukocyte antigen (HLA) class I molecules. Following hematopoietic stem cell transplantation for patients lacking Bw4, KIR3DL1-expressing NK cells from Bw4-positive donors can be alloreactive and eliminate tumor cells. However, KIR3DL1 alleles having T instead of C at nucleotide 320 (encoding leucine 86 instead of serine 86) are not expressed on the cell surface. Thus, not all individuals testing positive for KIR3DL1 are optimal donors for Bw4-negative recipients. Therefore, we developed a method for genotyping codon 86, which was validated by its perfect correlation with NK cell phenotype for 100 donors of diverse KIR3DL1/S1 genotype. We typed 600 donors and found that ∼12.2% had the KIR3DL1 gene, but did not express cell-surface KIR3DL1. By contrast, high-expressing allotypes were identified when haplotypes from four families with duplicated KIR3DL1/S1 genes were characterized at high resolution. Identifying donors who have KIR3DL1 but lack cell-surface KIR3DL1 would refine donor selection. With this technique, the number of individuals identified who may not be optimal donors for Bw4-negative patients increases by threefold, when compared with standard methods. Taken together, we propose that allele typing of killer cell Ig-like receptor (KIR) polymorphisms should become a standard practice when selecting donors.

• Authors: Claudia Alicata, Daniela Pende, Raffaella Meazza, Paolo Canevali, Fabrizio Loiacono, Alice Bertaina, Franco Locatelli, Neda Nemat-Gorgani, Lisbeth A Guethlein, Peter Parham, Lorenzo Moretta, Alessandro Moretta, Cristina Bottino, Paul J Norman, Michela Falco
• Journal: European journal of immunology (Eur J Immunol) Vol. 46 Issue 6 Pg. 1511-7 (06 2016) ISSN: 1521-4141 [Electronic] Germany
• PMID: 26990677 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Codon
• HLA-B Antigens
• HLA-Bw4 antigen
• KIR3DL1 protein, human
• Receptors, KIR3DL1
• Receptors, KIR3DS1

Topics

• Alleles
• Cell Membrane (metabolism)
• Codon
• Donor Selection
• Gene Expression
• Genotype
• HLA-B Antigens (immunology)
• Haplotypes
• Hematopoietic Stem Cell Transplantation
• Hematopoietic Stem Cells (immunology, metabolism)
• Humans
• Killer Cells, Natural (immunology, metabolism)
• Models, Biological
• Polymorphism, Single Nucleotide
• Receptors, KIR3DL1 (genetics, metabolism)
• Receptors, KIR3DS1 (genetics, metabolism)
• Transplantation, Homologous