HLA Mismatches and Hematopoietic Cell Transplantation: Structural Simulations Assess the Impact of Changes in Peptide Binding Specificity on Transplant Outcome

Overview

Journal Immunome Res

Publisher Omics Publishing Group

Specialty Allergy & Immunology

Date 2014 Feb 1

PMID 24482668

Citations 3

Authors

Chen Yanover

Effie W Petersdorf

Mari Malkki

Ted Gooley

Stephen Spellman

Andrea Velardi

Peter Bardy

Alejandro Madrigal

Jean-Denis Bignon

Philip Bradley

Affiliations

Soon will be listed here.

Abstract

The success of hematopoietic cell transplantation from an unrelated donor depends in part on the degree of Human Histocompatibility Leukocyte Antigen (HLA) matching between donor and patient. We present a structure-based analysis of HLA mismatching, focusing on individual amino acid mismatches and their effect on peptide binding specificity. Using molecular modeling simulations of HLA-peptide interactions, we find evidence that amino acid mismatches predicted to perturb peptide binding specificity are associated with higher risk of mortality in a large and diverse dataset of patient-donor pairs assembled by the International Histocompatibility Working Group in Hematopoietic Cell Transplantation consortium. This analysis may represent a first step toward sequence-based prediction of relative risk for HLA allele mismatches.

Citing Articles

HLA Matching in Unrelated Stem Cell Transplantation up to Date.

Furst D, Neuchel C, Tsamadou C, Schrezenmeier H, Mytilineos J Transfus Med Hemother. 2019; 46(5):326-336.

PMID: 31832058 PMC: 6876603. DOI: 10.1159/000502263.

16th IHIW: international histocompatibility working group in hematopoietic cell transplantation.

Petersdorf E, Malkki M, Hsu K, Bardy P, Cesbron A, Dickinson A Int J Immunogenet. 2013; 40(1):2-10.

PMID: 23279968 PMC: 3887040. DOI: 10.1111/iji.12022.

Genetics of graft-versus-host disease: the major histocompatibility complex.

Petersdorf E Blood Rev. 2012; 27(1):1-12.

PMID: 23182478 PMC: 3626414. DOI: 10.1016/j.blre.2012.10.001.

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