# Deconstructed T cell antigen recognition: Separation of affinity from bond lifetime

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2024 · $718,524

## Abstract

Abstract
Recognition of antigen is the first critical step required in triggering T cell survival, expansion, development of
effector functions, and transition to memory. In a joint project between the Evavold and Williams labs, we will
determine how T cell receptor (TCR) and peptide:MHC (pMHC) affinity, bond lifetimes, and force magnitude
define T cell phenotype. The proposed work is therefore impactful as it begins to delineate the role each of
these parameters play in the rich T cell biology associated with TCR signal strength. To date, the concept of
TCR strength of signal has generally been described with three-dimensional SPR affinity in mind and
measured via representative surface markers, pMHC tetramers, and functional readouts. In contrast to these
methods, our studies depend on the analysis of TCR and pMHC interactions at the surface of the cell
membrane using novel assays that define the in-situ two-dimensional contact that occurs between T cells and
APCs during antigen recognition. The preliminary work has discovered that bond lifetime and level of force as
opposed to affinity provides the major driving force for phenotypic fate. The three specific aims will redefine the
concept of TCR strength of signal, dissect affinity from bond lifetime, and determine outcomes of low affinity
TCRs during infection. Currently, the TCR affinity and bond lifetime for pMHC are unknown for many T cell
responses, limiting our knowledge on how T cell mediated responses are triggered and how affinity and bond
lifetime are translated into TCR strength of signal and effector phenotypes. Therefore, our work will prove
insightful by addressing the discrepancy between affinity based predictions and actual T cell functional
outcomes.

## Key facts

- **NIH application ID:** 10818594
- **Project number:** 5R01AI172253-02
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Brian D Evavold
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $718,524
- **Award type:** 5
- **Project period:** 2023-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10818594

## Citation

> US National Institutes of Health, RePORTER application 10818594, Deconstructed T cell antigen recognition: Separation of affinity from bond lifetime (5R01AI172253-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10818594. Licensed CC0.

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