# TI A AND B V GENE USAGE IN HUMAN T CELL MALIGNANCIES

> **NIH NIH R01** · DANA-FARBER CANCER INST · 1987 · $170,922

## Abstract

Human T-cell receptors have been defined on inducer, suppressor, and class
I and class II specific cytotoxic T lymphocytes as 90 kilodalton
T3-associated clonotypic molecules.  These are comprised of one 49 to
51-kilodalton alpha and one 43 kilodalton beta subunit, both disulfide
linked. Peptide map analysis studies suggested that each subunit is
comprised of constant and variable domains.  Moreover, the precise
molecular basis for this variability in the beta subunit has now been
defined by DNA cloning studies, showing that similar to immunoglobulin
heavy chain, specific V, D, J, and C segments fuse to form an active Ti
gene.  This process occurs in the thymus at an early stage of intrathymic
ontogeny (stage II).  However, surface expression of the T3-Ti complex is
restricted to a minor population of thymic lymphocytes (stage III).  The
ability to identify variable region genes encoding the Ti beta subunit of
the T-cell receptor (and shortly the Ti alpha subunit) makes possible, for
the first time, analysis of human T-cell malignancies at the clonal level.
Thus, it is now feasible to question the extent of clonal variability of
tumors within and among clinical types by examining the V genes which are
rearranged to form one of their active Ti subunits.  This can be related to
V gene utilization by "physiologic" T-cell and thymocyte populations.  Our
research will include:  (1) cloning and sequencing Ti beta V genes from a
variety of T-cell malignancies and performing frequency analysis of
utilization of these V genes within human thymus and peripheral T-cell
compartments; (2) examining the relationship of V genes employed by T-cell
acute lymphoblastic leukemias, lymphoblastic lymphomas, and Sezary syndrome
to determine whether there is restriction to a single clinical type of
malignancy; (3) producing monocloncal antibodies against synthetic peptides
corresponding to V gene sequences utilized by several of these tumor
populations for direct tissue distribution analysis; and (4) determining
whether restriction analysis of DNA from T-cell malignancies with Ti beta
probes will be of diagnostic utility.  An analogous set of experiments will
be performed with the Ti alpha probe as soon as it is available.  (AG)

## Key facts

- **NIH application ID:** 3179679
- **Project number:** 5R01CA040134-03
- **Recipient organization:** DANA-FARBER CANCER INST
- **SAM.gov UEI:** DPMGH9MG1X67
- **Principal Investigator:** ELLIS L REINHERZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $170,922
- **Award type:** 5
- **Project period:** 1985-08-01 → 1988-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3179679

## Citation

> US National Institutes of Health, RePORTER application 3179679, TI A AND B V GENE USAGE IN HUMAN T CELL MALIGNANCIES (5R01CA040134-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3179679. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*