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Identifying a minor histocompatibility antigen in mauritian cynomolgus macaques encoded by APOBEC3C

Weinfurter, Jason T., Graham, Michael E., Ericsen, Adam J., Matschke, Lea M., Llewellyn-Lacey, Sian, Price, David A., Wiseman, Roger W. and Reynolds, Matthew R. 2020. Identifying a minor histocompatibility antigen in mauritian cynomolgus macaques encoded by APOBEC3C. Frontiers in Immunology 11 , 586251. 10.3389/fimmu.2020.586251

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Allogeneic hematopoietic stem cell transplants can lead to dramatic reductions in human immunodeficiency virus (HIV) reservoirs. This effect is partially mediated by donor T cells recognizing lymphocyte-expressed minor histocompatibility antigens (mHAgs). The potential to mark malignant and latently infected cells for destruction makes mHAgs attractive targets for cellular immunotherapies. However, testing such HIV reservoir reduction strategies will likely require preclinical studies in non-human primates (NHPs). In this study, we used a combination of alloimmunization, whole exome sequencing, and bioinformatics to identify an mHAg in Mauritian cynomolgus macaques (MCMs). We mapped the minimal optimal epitope to a 10-mer peptide (SW10) in apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3C (APOBEC3C) and determined the major histocompatibility complex class I restriction element as Mafa-A1∗063, which is expressed in almost 90% of MCMs. APOBEC3C SW10-specific CD8+ T cells recognized immortalized B cells but not fibroblasts from an mHAg-positive MCM. These results provide a framework for identifying mHAgs in a non-transplant setting and suggest that APOBEC3C SW10 could be used as a model antigen to test mHAg-targeted therapies in NHPs.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Frontiers Media
ISSN: 1664-3224
Date of First Compliant Deposit: 13 July 2021
Date of Acceptance: 8 September 2020
Last Modified: 31 Jan 2022 07:25

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