Lucas, JAM;
Marsh, SGE;
Mayor, NP;
(2025)
An In-Depth Review of the Genetics of the Non-Classical HLA Class I Gene HLA-E and Its Effects on Haematopoietic Cell Transplant Outcomes.
HLA
, 106
(2)
, Article e70344. 10.1111/tan.70344.
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Abstract
HLA-E is a non-classical HLA class I gene with limited reported genetic variability and few published studies into full-gene sequencing or population allele frequencies. Two protein variants, HLA-E*01:01 and HLA-E*01:03, are very common, accounting for 94%–100% of observed alleles in most studies performed to date. Frequently utilised exon-based sequencing strategies have led to the assumption of HLA-E being a near bi-allelic gene; however, recent full-gene sequencing studies have shown a greater degree of genetic variability than initially imagined. We carried out a literature review of HLA-E genotype and ethnicity data, which suggested HLA-E*01:03 is more common in Asian and, in particular, East Asian populations. Furthermore, HLA-E*01:03:02 is more frequently observed than HLA-E*01:03:01 in European and American populations, whereas HLA-E*01:03:01 is found at higher frequencies in Asian populations. It has been proposed that HLA-E may have a role in Haematopoietic Cell Transplantation (HCT) due to its interaction with NK and CD8<sup>+</sup> T cells and its non-canonical peptide binding repertoire. Here we also review published literature into the effects of HLA-E genetics on HCT outcomes. Heterogeneity between cohorts muddies the waters; hence, studies report confounding effects of HLA-E genotype and matching on HCT outcomes. The need for further HLA-E sequencing of larger cohorts is evident to gain useful insight into the true genetic variability of HLA-E and its impact on HCT.
| Type: | Article |
|---|---|
| Title: | An In-Depth Review of the Genetics of the Non-Classical HLA Class I Gene HLA-E and Its Effects on Haematopoietic Cell Transplant Outcomes |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1111/tan.70344 |
| Publisher version: | https://doi.org/10.1111/tan.70344 |
| Language: | English |
| Additional information: | Copyright © 2025 The Author(s). HLA: Immune Response Genetics published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | diversity, genetics, haematopoietic cell transplant, HLA-E, non-classical HLA |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10212493 |
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