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Investigating ultra-small AIDS virus reservoirs

An essential question for HIV cure research is: how small must HIV reservoirs be to achieve sustained remission without antiretroviral drugs? While antiretroviral therapy (ART) effectively controls HIV replication, it’s not a cure. Therefore, significant efforts are focused on developing treatments to reduce viral reservoirs and enhance antiviral immunity. However, a persistent question in HIV research is how much these interventions need to reduce viral reservoirs to achieve meaningful periods of HIV remission after stopping ART. To explore this, we developed a model to precisely control the size of latent reservoirs in rhesus macaques. This model helps us understand the impact of small viral reservoirs on the timing of viral rebound and the ability of antiviral immune responses to control virus replication after ART withdrawal.

Isolating monoclonal antibodies

We developed a new approach to cloning antibodies from individual B cells. With this method, we are isolating monoclonal antibodies that target specific host proteins, including macaque major histocompatibility complex (MHC) and killer-immunoglobulin-like receptor (KIR) molecules. Our anti-MHC antibodies are available through the Nonhuman Primate Reagent Resource. Additionally, we offer a  service to isolate monoclonal antibodies through the WNPRC Immunology Services unit.

Mapping minor histocompatibility antigens

Minor histocompatibility antigens (mHAgs) are MHC-bound peptides on cell surfaces that can stimulate immune responses after organ transplants and arise from genetic differences between the organ donor and recipients. Identifying mHAgs is challenging due to the size of the genome and the number of potential differences between individuals. We have developed a process to map mHAg in Mauritian cynomolgus macaques using a combination of cellular immunology, genomics, and bioinformatics.

Our paper identifying the first nonhuman primate mHAg.


The conceptual outline for mapping mHAgs in Mauritian cynomolgus macaques. (1) exome sequence the genomes of MHC-identical MCM, (2) generate bulk mHAg-reactive T cell lines, (3) single-cell sort mHAg-reactive T-cell clones, (4) test clones against a panel of BLCL from exome sequenced MCM, (5) group into BLCL that induce clone reactivity or non-reactivity, and (6) segregation analysis to identify candidate mHAgs.