# Project 2 - B cell antigen receptor structure and antigen-BCR interaction dynamics

> **NIH AI U54** · DUKE UNIVERSITY · 2026 · $377,305

## Abstract

Project Summary/Abstract – Project 2 Structural analysis of how HIV-1 Envelope (Env) interacts with antigen receptor on B cells (BCR) to initiate B cell signaling and activation is key to understanding antibody responses against HIV protein immunogens. Recent studies of the organization of the BCR complex on the cell membrane supports a model in which BCRs exist in different signaling states that require definition in structural terms. We hypothesize the following distinct states of the BCR complex – 1) “signaling-inhibited’, 2) signaling-competent and 3) ‘signaling-disrupted’. Advances in HIV-1 Env design including those that target germline precursors have led to the development of Env immunogens as potential candidates for HIV vaccines. How BCRs of distinct specificities and signaling-states interact with Env protein immunogens that trigger signaling and activate these cells are not clearly understood. The overall goal of the project is to define BCR-antigen structures with specificity of broadly neutralizing antibodies (bnAb), non-canonical glycan-binding bnAbs and to-be isolated autologous neutralizing antibodies (anAb). In this project, we will perform biophysical/biochemical, structural and immunological analyses to define properties of HIV Env-BCR interactions for activation of B cells expressing bnAb or germline precursor BCRs. In Aim 1, we will perform Cryo-EM and molecular dynamic simulation analyses to define structures of antigen- liganded BCR complex with specificities of autologous or broadly neutralizing HIV-1 antibodies. In addition, we will define the structures of BCRs with specificities of glycan-binding bnAbs that present non-canonical Fab configurations (I-shaped versus Y-shaped). In Aim 2, we will study specificity of bnAb precursors with disrupted proximal signaling and determine whether such BCRs show distinct cell surface interaction dynamics with Env proteins. Studies in Aim 3 will define antigen-BCR interaction parameters that enhance B c

## Key facts

- **NIH application ID:** 11397295
- **Project number:** 5U54AI170752-05
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** S. Munir  ALAM
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** AI
- **Fiscal year:** 2026
- **Award amount:** $377,305
- **Award type:** 5
- **Project period:** 2022-06-14T00:00:00 → 2027-03-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11397295

## Citation

> US National Institutes of Health, RePORTER application 11397295, Project 2 - B cell antigen receptor structure and antigen-BCR interaction dynamics (5U54AI170752-05). Retrieved via AI Analytics 2026-07-04 from https://api.ai-analytics.org/grant/nih/11397295. Licensed CC0.

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