# KIR and MHC Class I Immunogenetics in SIV Infection

> **NIH NIH R37** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $696,522

## Abstract

PROJECT SUMMARY
Natural killer (NK) cells provide a critical early defense against viral pathogens by virtue of their ability to
recognize and kill virus-infected cells without prior antigenic stimulation. This is accomplished in part through
interactions between two highly polymorphic molecules; the killer-cell immunoglobulin-like receptors (KIRs) on
NK cells and their MHC class I ligands on target cells. KIR and HLA class I polymorphisms can have profound
effect on the course of HIV-1 infection and the efficacy of NK cell-based therapies for eradicating virus-infected
cells; however, animal studies to address underlying immunological mechanisms have been limited by our
understanding of KIR-MHC class I interactions in nonhuman primate models. Over the previous funding period,
we identified MHC class I ligands for five rhesus macaque KIRs and revealed a role for viral peptides in
suppressing NK cell activation as a potential mechanism of immune evasion. We also observed highly dynamic
changes in NK cell responses to SIV infection of KIR- and MHC class I-defined macaques, including an
enrichment of NK cells regulated by Bw4 ligands in lymphoid tissues that support high levels of virus
replication. Here we build on these studies to investigate specific hypotheses concerning the influence of viral
peptides on NK cell responses to virus-infected cells and the contribution of NK cells that recognize Bw4
ligands to the containment of immunodeficiency virus infection.
In Aim 1, we will define MHC class I ligands and isolate antibodies for the most common rhesus macaque
KIRs. This aim builds on recent studies to provide a broader knowledge base and key reagents for studying NK
cell responses in the rhesus macaque. In Aim 2, we will investigate the effects of viral peptides bound by MHC
class I ligands on NK cell recognition of virus-infected cells. We will determine the extent to which the
suppression of NK cell responses by viral peptides that stabilize MHC class I binding to inhibitory KIRs is a
common phenomenon or a unique property of certain KIR-MHC class I pairs, and whether peptides derived
from endogenously expressed viral antigens can also affect NK cell activity against virus-infected cells. In Aim
3, we will assess the contribution of a population of NK cells expressing a KIR specific for Bw4 ligands to the
containment of virus replication in animals by depleting these cells with a KIR-specific antibody prior to SIV
infection. These unprecedented studies will provide a better understanding of the functional effects of KIR-
MHC class I interactions on NK cell responses to immunodeficiency virus infection, including the role of viral
peptides in NK cell recognition of virus-infected cells and the impact of a dominant population of NK cells
regulated by Bw4 ligands on SIV pathogenesis.

## Key facts

- **NIH application ID:** 9815950
- **Project number:** 5R37AI095098-08
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** David T Evans
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $696,522
- **Award type:** 5
- **Project period:** 2011-11-14 → 2023-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9815950

## Citation

> US National Institutes of Health, RePORTER application 9815950, KIR and MHC Class I Immunogenetics in SIV Infection (5R37AI095098-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9815950. Licensed CC0.

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