CHARACTERIZATION OF THREE NEW T LYMPHOCYTE-SPECIFIC GENE

Project: Research project

Project Details

Description

We have developed a protocol which allowed us to isolated broad
representation of T-lymphocyte subset-specific cDNAs, and
applied the method to the analysis of ConA-stimulated cloned Th
and CTL cDNA libraries. Sixteen previously unrecognized T cell
specific genes have been isolated, in addition to seven known T-
cell genes. Three of the sixteen genes were expressed in both Th
and CTL, seven were expressed in only Th and six only in CTL.
The 16 genes were further characterized according to the
expression pattern after treatment with ConA-, IL-2, T-cell
receptor antibody or cyclosporin A. Nuclotide sequence analyses
identified five of these genes as corresponding to recently
described genes of known and unknown functions. The objective
of the present proposal is to demonstrate the functions of three of
the above genes which were selected because they are inducible
by ConA preferentially in Th and appear to represent new soluble
T-cell mediators. The strategy will be to prepare antibodies to
each of the gene products which recognize the corresponding
native proteins using oligopeptides or E. coli recombinant proteins
as antigens. Next, the gene products will be produced in the
purified from eukaryotic expression systems, which may simulate
closely the natural product. The antibodies specific to each of
the three cDNA products and the purified recombinant proteins
will then be utilized to determine the biologic function(s) of each
gene product. The investigations planned include receptor binding
studies to identify which cells carry receptors to these molecules,
and to demonstrate their functions using various immunological
assays. To supplement the in vitro immunological assays, mouse
mutants with various immunological disorders will be screened by
the cDNA probes to identify if such mutants carry abnormalities
of the corresponding genes. A long term objective is to identify
the human homologue of each of the molecules and to seek
clinical applications for human immunodeficiency and other
diseases such as human malignancies and AIDS. The present
investigation could present a model study for the demonstration
of functions and a clinical applications of unknown molecules that
have been identified at the nucleic acid level.
StatusFinished
Effective start/end date9/1/881/31/00

Funding

  • National Institutes of Health

ASJC

  • Medicine(all)
  • Immunology and Microbiology(all)

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