Hematopoietic stem cell transplantation

Improving alloreactive Bw4 donor selection by genotyping codon 86 of KIR3DL1/S1

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

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1511-1517
Number of pages7
JournalEuropean Journal of Immunology
Volume46
Issue number6
DOIs
Publication statusPublished - Jun 1 2016

Fingerprint

Donor Selection
Hematopoietic Stem Cell Transplantation
Codon
Tissue Donors
Natural Killer Cells
Alleles
Natural Killer Cell Receptors
HLA Antigens
Leucine
Serine
Haplotypes
Genes
Epitopes
Nucleotides
Genotype
Phenotype

Keywords

  • Donor selection
  • HLA haploidentical hematopoietic stem cell transplantation
  • Killer cell Ig-like receptor (KIR)
  • Natural killer (NK) cell
  • Next-generation sequencing

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Hematopoietic stem cell transplantation : Improving alloreactive Bw4 donor selection by genotyping codon 86 of KIR3DL1/S1. / Alicata, Claudia; Pende, Daniela; Meazza, Raffaella; Canevali, Paolo; Loiacono, Fabrizio; Bertaina, Alice; Locatelli, Franco; Nemat-Gorgani, Neda; Guethlein, Lisbeth A.; Parham, Peter; Moretta, Lorenzo; Moretta, Alessandro; Bottino, Cristina; Norman, Paul J.; Falco, Michela.

In: European Journal of Immunology, Vol. 46, No. 6, 01.06.2016, p. 1511-1517.

Research output: Contribution to journalArticle

Alicata, Claudia ; Pende, Daniela ; Meazza, Raffaella ; Canevali, Paolo ; Loiacono, Fabrizio ; Bertaina, Alice ; Locatelli, Franco ; Nemat-Gorgani, Neda ; Guethlein, Lisbeth A. ; Parham, Peter ; Moretta, Lorenzo ; Moretta, Alessandro ; Bottino, Cristina ; Norman, Paul J. ; Falco, Michela. / Hematopoietic stem cell transplantation : Improving alloreactive Bw4 donor selection by genotyping codon 86 of KIR3DL1/S1. In: European Journal of Immunology. 2016 ; Vol. 46, No. 6. pp. 1511-1517.
@article{6422dfd6b55e43ce9628bbd9b801ef82,
title = "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.",
keywords = "Donor selection, HLA haploidentical hematopoietic stem cell transplantation, Killer cell Ig-like receptor (KIR), Natural killer (NK) cell, Next-generation sequencing",
author = "Claudia Alicata and Daniela Pende and Raffaella Meazza and Paolo Canevali and Fabrizio Loiacono and Alice Bertaina and Franco Locatelli and Neda Nemat-Gorgani and Guethlein, {Lisbeth A.} and Peter Parham and Lorenzo Moretta and Alessandro Moretta and Cristina Bottino and Norman, {Paul J.} and Michela Falco",
year = "2016",
month = "6",
day = "1",
doi = "10.1002/eji.201546236",
language = "English",
volume = "46",
pages = "1511--1517",
journal = "European Journal of Immunology",
issn = "0014-2980",
publisher = "wiley",
number = "6",

}

TY - JOUR

T1 - Hematopoietic stem cell transplantation

T2 - Improving alloreactive Bw4 donor selection by genotyping codon 86 of KIR3DL1/S1

AU - Alicata, Claudia

AU - Pende, Daniela

AU - Meazza, Raffaella

AU - Canevali, Paolo

AU - Loiacono, Fabrizio

AU - Bertaina, Alice

AU - Locatelli, Franco

AU - Nemat-Gorgani, Neda

AU - Guethlein, Lisbeth A.

AU - Parham, Peter

AU - Moretta, Lorenzo

AU - Moretta, Alessandro

AU - Bottino, Cristina

AU - Norman, Paul J.

AU - Falco, Michela

PY - 2016/6/1

Y1 - 2016/6/1

N2 - 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.

AB - 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.

KW - Donor selection

KW - HLA haploidentical hematopoietic stem cell transplantation

KW - Killer cell Ig-like receptor (KIR)

KW - Natural killer (NK) cell

KW - Next-generation sequencing

UR - http://www.scopus.com/inward/record.url?scp=84973597876&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84973597876&partnerID=8YFLogxK

U2 - 10.1002/eji.201546236

DO - 10.1002/eji.201546236

M3 - Article

VL - 46

SP - 1511

EP - 1517

JO - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

IS - 6

ER -