# CTL IMMUNE RESPONSE TO INGESTED TOXOPLASMA

> **NIH NIH R01** · MICHAEL REESE HOSPITAL · 1993 · $288,742

## Abstract

To better understand pathogenesis and protection in toxoplasmosis,
proteins which elicit cytolytic T lymphocytes (CTL) will be further
characterized and tested for ability to protect.

Toxoplasma peptide which stimulates protective CTL when bound to MHC
Class I Ld (called TgLdP) will be identified.  This will be accomplished
by affinity chromatography, acid disruption of Ld-peptide complex, HPLC
isolation, NMR and sequencing.  T2-Ld cells express Ld on their surface
and efficiently bind Ld restricted peptides extracellularly.  MHC bound
peptides unique to infected cells will be tested for biological activity
measured as ability to render T2-Ld cells targets for anti-Toxoplasma
CTL.  The protein from which this peptide originates (TgLd) will be
identified, either by comparison with known T. gondii protein sequences
or by screening our T. gondii DNA library with antibody to multiple
antigenic peptides and sequencing the gene identified.

As an alternative approach for identifying TgLdP, T. gondii peptides with
the Ld motif will be tested for ability to render T2-Ld cells targets for
T. gondii specific CTL lines and a protective CTL clone.  When a peptide
is found to be a CTL target, it will be studied for ability to elicit
protective CTL when administered as a lipopeptide.

Immunoelectronmicroscopy with antibodies to TgLd will establish its
location within the parasite and also its movement from the
parasitophorous vacuole into the host cell cytoplasm and through a MHC
Class I presentation pathway.

Effect of CTL on intracellular T. gondii will be determined.  Mechanism
of CTL effect will be studied by immunizing perforin deficient mice and
determining if they can generate T. gondii specific CTL.

To determine if human CTL recognize T. gondii immunodominant proteins and
identify their MHC restriction, human CTL responses to TgLd or other
Toxoplasma proteins will be tested by generating target cells with
defined MHC Class I haplotypes which express selected T. gondii proteins.
To identify whether there are resistant human MHC haplotypes, similar to
murine Ld, susceptible H-2b mice expressing human MHC Class I transgenes
will be tested for their resistance to parasitemia and cyst formation.

Proteins which elicit protective CTL will be studied for ability to
protect using our models of peroral and congenital infection.  Effect of
administration with adjuvant or expression by an avian pox construct on
duration of CTL activity and protection will be compared.  These proteins
will be tested first for superantigen or mitogenic activity as this would
impact on their use in protective preparations.

The proposed studies will define protein(s) that confer protection
against T. gondii by eliciting CTL.

## Key facts

- **NIH application ID:** 3126925
- **Project number:** 2R01AI016945-13
- **Recipient organization:** MICHAEL REESE HOSPITAL
- **Principal Investigator:** Rima L McLeod
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $288,742
- **Award type:** 2
- **Project period:** 1980-07-01 → 1998-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3126925

## Citation

> US National Institutes of Health, RePORTER application 3126925, CTL IMMUNE RESPONSE TO INGESTED TOXOPLASMA (2R01AI016945-13). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3126925. Licensed CC0.

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