# Advancing MHC-E-Restricted T cells as a Universal Immunotherapeutic

> **NIH NIH K01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $111,415

## Abstract

PROJECT SUMMARY
At the end of 2018, the United Nations estimated that 38 million people were living with HIV/AIDS with 1.7 million
new infections. Although a prophylactic vaccine would do much to halt this epidemic, attaining durable remission
among HIV-1 infected individuals would not only curb new infections but also dramatically reduce the societal
burden required to maintain continuous life-long ART treatment for so many. Unfortunately, cellular therapeutic
interventions to purge HIV-1 infected cells in vivo are relatively limited. MHC-E-restricted CD8+ T cells may
represent a universally applicable therapeutic approach. With only two nearly identical HLA-E alleles expressed
in the majority of the human population, MHC-E-restricted HIV-specific T cell receptors could be utilized as a
donor unrestricted therapeutic reagent. Strain 68-1 RhCMV vectors encoding SIV antigens (RhCMV/SIV) are
capable of stringently controlling SIV replication, and that protection is dependent on the induction of SIV-specific
MHC-E-restricted CD8+ T cells. Despite its prophylactic utility, RhCMV induces an effector memory CD8+ T cell
response directed at portals of HIV/SIV entry not secondary lymphoid tissues where the bulk of SIV resides
during chronic infection. Prior studies have demonstrated that CD8+ T cells transduced with CXCR5 traffic to the
lymph node B-cell follicle a key site of the SIV/HIV reservoir. In this proposal, we will sequence full length MHC-
E-restricted T cell receptors from RhCMV/SIV vaccinated macaques that stringently controlled SIV replication.
We will generate autologous CD8+ T cell transductants expressing these MHC-E-TCR and CXCR5 and infuse
them into SIV-infected ART-suppressed rhesus macaque. After release of ART, we will use a combination of
tissue staining and single-cell RNA sequencing to assess whether these transductants traffic to the B-cell follicle
and activate in response to infected virus-producing cells. In addition, we will assess whether MHC-E-TCR
transductants delay viral rebound. The experiments outlined in this project may form the basis of a new
alternative universal therapeutic intervention for those infected with HIV-1.

## Key facts

- **NIH application ID:** 10015733
- **Project number:** 1K01OD029804-01
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Shaheed A. Abdulhaqq
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $111,415
- **Award type:** 1
- **Project period:** 2020-04-01 → 2020-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10015733

## Citation

> US National Institutes of Health, RePORTER application 10015733, Advancing MHC-E-Restricted T cells as a Universal Immunotherapeutic (1K01OD029804-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10015733. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*