# Viral adaptation to CD4 T cell responses and the impact on HIV immunity

> **NIH NIH K08** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $195,264

## Abstract

ABSTRACT
Robust CD4 T cell responses are likely to be critical for any protective HIV vaccine through their multifaceted
support of immune effectors, but as the primary targets of HIV infection their contribution to host immunity has
been relatively understudied. We have recently demonstrated CD4 T cell immune responses are capable of
driving viral adaptation, but the mechanism of this activity and its relevance to overall disease pathogenesis is
unknown. A CD4 T cell subset, the T follicular helper cell (Tfh), has become a focus of investigation for
its role
in B cell differentiation and maturation as well as its facilitation of pathogen-specific high-affinity neutralizing
antibody responses.
 CD4 T cells also have cytotoxic potential, a phenotype we have shown is compromised by
single amino acid changes in viral epitopes suggesting a role in viral escape. We hypothesize viral
adaptation compromises the immunologic functions of CD4 T cells resulting in a survival benefit for
HIV and impacting the clinical course of disease. We will test this hypothesis in three separate aims:
Specific Aim 1: Through TCR sequencing, determine the effects of viral adaptation on CD4 T cells
ability to bind antigen and appropriately activate in response to stimulation.
Specific Aim 2: Define the impact of viral adaptation on CD4 T cell effector functions as expressed by
cytotoxic capacity and expansion of the Tfh phenotype.
Specific Aim 3: Determine whether persons infected with highly adapted virus have accelerated HIV-1
clinical disease progression.
The proposed aims will reveal the mechanism underlying viral adaptation to CD4 T cell immune pressure and
the impact on disease. To support these efforts, I have developed a collaborative program that will provide
access to primary tissues from deceased-donors, offering a unique opportunity to corroborate findings
observed in peripheral blood samples with those from tissue-derived lymphocytes. The mentorship team
combines a strong record of trainee development and expertise in the areas most relevant to the planned
experiments. I also present a curriculum designed to enhance my immunologic knowledge, technical
repertoire, statistical knowledge and professional development. The proposal will facilitate development of the
skills necessary to identify clinically relevant research questions and advance the understanding of immunity to
HIV and other chronic viral infections.

## Key facts

- **NIH application ID:** 9955167
- **Project number:** 5K08AI129705-04
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Nathaniel Bernard Erdmann
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $195,264
- **Award type:** 5
- **Project period:** 2017-07-14 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9955167

## Citation

> US National Institutes of Health, RePORTER application 9955167, Viral adaptation to CD4 T cell responses and the impact on HIV immunity (5K08AI129705-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9955167. Licensed CC0.

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