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Identification of a lymphocyte minor histocompatibility antigen in Mauritian cynomolgus macaques

By Jason T Weinfurter, Michael E Graham, Adam J. Ericsen, Lea M Matschke, Sian Llewellyn-Lacey, David A. Price, Roger W. Wiseman, Matthew R. Reynolds

Posted 12 Jun 2020
bioRxiv DOI: 10.1101/2020.06.10.145250

Allogeneic hematopoietic stem cell transplantation can lead to dramatic reductions in human immunodeficiency virus (HIV) reservoirs. This effect is mediated in part by donor T cells that recognize 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 nonhuman primates (NHPs). In this study, we used a combination of alloimmunization, whole exome sequencing, and bioinformatics to identify a 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 (APOBEC3) 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 a mHAg positive MCM. These results collectively provide a framework for identifying mHAgs in a nontransplant setting and suggest that APOBEC3C SW10 could be used as a lymphocyte-restricted model antigen in NHPs to test various mHAg-targeted immunotherapies. ### Competing Interest Statement The authors have declared no competing interest.

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