Identifying a Minor Histocompatibility Antigen in Mauritian Cynomolgus Macaques Encoded by APOBEC3C

Area of Science:

• Immunology
• Virology
• Genetics

Background:

• Allogeneic hematopoietic stem cell transplants reduce human immunodeficiency virus (HIV) reservoirs, partly via donor T cells recognizing minor histocompatibility antigens (mHAgs).
• mHAgs are potential targets for cellular immunotherapies to eliminate malignant and latently infected cells.
• Preclinical studies in non-human primates (NHPs) are essential for testing HIV reservoir reduction strategies.

Purpose of the Study:

• To identify a minor histocompatibility antigen (mHAg) in Mauritian cynomolgus macaques (MCMs) for preclinical research.
• To establish a framework for identifying mHAgs in non-transplant settings.
• To evaluate a specific mHAg as a model antigen for testing targeted therapies in NHPs.

Main Methods:

• Alloimmunization, whole exome sequencing, and bioinformatics were employed to identify an mHAg in MCMs.
• The minimal optimal epitope was mapped to a 10-mer peptide (SW10) within apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3C (APOBEC3C).
• The major histocompatibility complex class I restriction element was identified as Mafa-A1*063, prevalent in MCMs.

Main Results:

• An mHAg, APOBEC3C SW10, was identified in Mauritian cynomolgus macaques.
• Mafa-A1*063 was determined as the restriction element for this mHAg, present in nearly 90% of MCMs.
• APOBEC3C SW10-specific CD8+ T cells recognized mHAg-positive B cells but not fibroblasts.

Conclusions:

• This study provides a method for identifying mHAgs outside of transplant contexts.
• APOBEC3C SW10 serves as a valuable model antigen for advancing mHAg-targeted therapies in NHP models.
• The findings support the development of novel cellular immunotherapies for HIV reservoir eradication.