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Lack of recognition of HLA class I mismatches outside α1/α2 domains by CD8+ alloreactive T lymphocytes: the HLA-B44 paradigm


Bettens, F; Schanz, U; Tiercy, J M (2013). Lack of recognition of HLA class I mismatches outside α1/α2 domains by CD8+ alloreactive T lymphocytes: the HLA-B44 paradigm. Tissue Antigens, 6(81):414-418.

Abstract

Transplantation with hematopoietic stem cells (HSC) from a donor with a single human leukocyte antigen (HLA) mismatch can be proposed to those patients lacking an HLA identical sibling donor or an unrelated donor matched for the HLA-A, -B, -C, DRB1, DQB1 loci. Incompatibilities at HLA classes I and II loci are associated with an increased risk of graft-versus-host disease (GVHD) and mortality, although no consensus exists yet on the relative importance of specific allele disparities on clinical outcome. Donor search algorithms are now complicated by the growing number of new HLA alleles, in particular those that differ outside the peptide-binding site of the HLA molecules. We report here an in vitro cellular assay to quantify CD8+CD137+ alloreactive cytotoxic T lymphocytes (CTLs) in a one-way mixed lymphocyte reaction. Two unique combinations with a single HLA mismatch in the HLA-B44 serotype differing by one amino acid in the α3 domain were investigated. We show that the B*44:27 versus B*44:02 mismatch was not recognized by CTLs in both directions. At days 10 and 20, the frequency of CD8+CD137+T cells was comparable to that measured in the autologous stimulation (0.3-3.9%). A B*44:02 versus B*44:03 mismatch was, however, well recognized at day 10 (7.2%) and day 20 (17.8%). This is the first demonstration that a single HLA-B mismatch involving a residue outside the peptide-binding site is not recognized in an in vitro functional assay and may probably be considered as a permissive incompatibility in vivo.

Abstract

Transplantation with hematopoietic stem cells (HSC) from a donor with a single human leukocyte antigen (HLA) mismatch can be proposed to those patients lacking an HLA identical sibling donor or an unrelated donor matched for the HLA-A, -B, -C, DRB1, DQB1 loci. Incompatibilities at HLA classes I and II loci are associated with an increased risk of graft-versus-host disease (GVHD) and mortality, although no consensus exists yet on the relative importance of specific allele disparities on clinical outcome. Donor search algorithms are now complicated by the growing number of new HLA alleles, in particular those that differ outside the peptide-binding site of the HLA molecules. We report here an in vitro cellular assay to quantify CD8+CD137+ alloreactive cytotoxic T lymphocytes (CTLs) in a one-way mixed lymphocyte reaction. Two unique combinations with a single HLA mismatch in the HLA-B44 serotype differing by one amino acid in the α3 domain were investigated. We show that the B*44:27 versus B*44:02 mismatch was not recognized by CTLs in both directions. At days 10 and 20, the frequency of CD8+CD137+T cells was comparable to that measured in the autologous stimulation (0.3-3.9%). A B*44:02 versus B*44:03 mismatch was, however, well recognized at day 10 (7.2%) and day 20 (17.8%). This is the first demonstration that a single HLA-B mismatch involving a residue outside the peptide-binding site is not recognized in an in vitro functional assay and may probably be considered as a permissive incompatibility in vivo.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Hematology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:June 2013
Deposited On:18 Nov 2013 10:22
Last Modified:16 Feb 2018 18:24
Publisher:Wiley-Blackwell
ISSN:0001-2815
OA Status:Closed
Publisher DOI:https://doi.org/10.1111/tan.12102
PubMed ID:23488546

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