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HLA mismatches that are identical for the antigen recognition domain are less immunogenic

Bone Marrow Transplantation volume 53, pages 729–740 (2018)Cite this article

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Abstract

For hematopoietic stem cell transplantation (HCT) HLA 10/10 (HLA-A, B, C, DRB1, DQB1) matched donors are optimal, but are not available for all patients. The identification of permissive/non-immunogenic mismatches may improve the outcome of HLA mismatched transplants. We hypothesize that HLA alleles identical within the antigen recognition domain (ARD), but mismatched outside the peptide binding groove or α-helices are often permissive mismatches. We evaluated the functional impact of non-ARD mismatches by performing in vitro functional T cell assays. Cytotoxic T Lymphocyte precursor assays were performed for 23 HLA class I mismatches and 96% (22 out of 23) were negative. Mixed lymphocyte reaction assays were conducted on 10 HLA class II mismatches and all were negative. However, 4 out of 10 combinations were positive in the Elispot and all involved one direction: a DRB1*14:01/DRB3*02:01 responder against a DRB1*14:54/DRB3*02:02 stimulator. These positive responses were confirmed by Primed Lymphocyte Testing and the DRB1* mismatch seemed to be responsible for the response. In conclusion, HLA mismatches with amino-acid differences outside the ARD are not very immunogenic. However, in some cases weak T cell reactivity in vitro can be observed. The impact of these responses on clinical outcome of HCT remains to be established.

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Acknowledgements

The CIBMTR is supported by Office of Naval Research Grants N00014-14-1-0028 and N00014-15-1-0848. The views expressed in this article do not reflect the official policy or position of the Department of the Navy, the Department of Defense, or any other agency of the US government.

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Authors and Affiliations

  1. Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands

    Dave Roelen, Yvonne de Vaal, Frans Claas & Machteld Oudshoorn

  2. Center for International Blood and Marrow Transplant Research, Minneapolis, MN, USA

    Cynthia Vierra-Green, Stephanie Waldvogel & Stephen Spellman

  3. Matchis Foundation, Leiden, The Netherlands

    Machteld Oudshoorn

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  1. Dave Roelen
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  2. Yvonne de Vaal
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  6. Frans Claas
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  7. Machteld Oudshoorn
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Correspondence to Dave Roelen.

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Roelen, D., de Vaal, Y., Vierra-Green, C. et al. HLA mismatches that are identical for the antigen recognition domain are less immunogenic. Bone Marrow Transplant 53, 729–740 (2018). https://doi.org/10.1038/s41409-018-0108-6

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