# T CELL RECEPTOR GENE REPERTOIRE IN AGING

> **NIH NIH R01** · SCRIPPS RESEARCH INSTITUTE, THE · 1993 · $252,298

## Abstract

DESCRIPTION:  (Investigator's abstract):  A theory of aging hypothesizes
that immunologic senescence and dysregulation leads to autoimmune tissue
damage that is of major importance in the aging process.  Thymic involution
and a number of immunologic dysfunctions, particularly in T-cells, have
been associated with aging, but the mechanisms leading to these
manifestations are unknown.  The overall objective of this proposal is to
determine whether aging and thymic involution are associated with changes
in T-cell antigen receptor (TCR) variable (V) region gene repertoire,
particularly abnormalities in intrathymic positive and negative selection
processes.  The proposed studies will assess total TCR Vbeta expression
patterns in primary lymphoid organs, and T-cell subsets thereof, of young
and aged murine inbred strains of several H-2 and Mls backgrounds using a
qualitative and quantitative RNAase protection assay.  The "idiotypic"
repertoire of such mice to defined T-cell-dependent epitopes will also be
assessed by cloning TCR Valpha and Vbeta elements from corresponding T-cell
hybridomas.  Self-renewal capacity and re-emergence of Vbeta clonotypes
upon their elimination with Vbeta-specific monoclonal antibodies in
thymectomized or non-thymectomized young and aged mice will be evaluated,
and the effects of environmental "superantigens" in shaping in vivo the TCR
repertoire of mice with involuted thymuses will be ascertained.  The
contribution of the thymic microenvironment versus bone marrow precursor
composition in age-related TCR repertoire changes, if any, will be examined
in irradiated mice of various ages reconstituted with syngeneic bone
marrows from aged mice to inhibit autoimmune disease development in
appropriate murine models will be compared.  Moreover, TCR Vbeta gene
repertoires in peripheral lymphocytes of humans of both sexes and of
various ages will be analyzed.

## Key facts

- **NIH application ID:** 3121282
- **Project number:** 5R01AG009430-03
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **SAM.gov UEI:** PHZJFZ32NKH4
- **Principal Investigator:** Argyrios N Theofilopoulos
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $252,298
- **Award type:** 5
- **Project period:** 1991-02-01 → 1994-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3121282

## Citation

> US National Institutes of Health, RePORTER application 3121282, T CELL RECEPTOR GENE REPERTOIRE IN AGING (5R01AG009430-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3121282. Licensed CC0.

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