# TRANSPLANTATION ANTIGENS--EXPRESSION AND FUNCTION

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 1993 · $222,902

## Abstract

The functions of the highly polymorphic classical transplantation
antigens in graft rejection and in defense against viral infections have
long been well recognized.  In contrast, the properties and the
physiological effects of the much larger family of nonpolymorphic class
I-like MHC molecules are still unknown.  The structural similarities of
the two classes of polypeptides suggest that the nonclassical MHC
molecules may bind self or nonself peptides and may interact with T-cell
receptors.  The identification of the proteins from which the putative
peptides are derived and the recognition of the effects that they may
have on cells with which they interact represent major challenges as they
may lead to the formulation of new concepts in immunology.

Qa-2 molecules are among the best characterized nonclassical
transplantation antigens in the mouse.  They exist in two forms:  1)
glycophosphatidyl-inositol (GPI) linked membrane antigens which are
predominantly expressed on lymphoid derived cells and can serve as
targets for cytotoxic cells as well as transducers of activation signals
in T cells and 2) soluble Qa-2 molecules which are released into the
serum and have been hypothesized to induce activation or anergy states.
The "switching" from membrane to soluble form is inducible in vitro by
cell activation and involves alternative splicing of exon 5 of the Qa-2
gene.

The specific aims of this proposal are:

1.   To identify the cis-acting elements of the Qa-2 genes that control
     alternative splicing of exon 5.

2.   To test a hypothesis that various regimens and signals inducing
     activation of immune system (i.e., lead to the alternative splicing
     of Qa-2 mRNA and secretion of soluble Qa-2 molecules in vivo, and
     to identify the major Qa-2 expressing cell subsets participating in
     different responses.

3.   To sequence the peptides bound to the secreted and GPI-linked Qa-2
     molecules in order to identify the self-antigens presented by the
     two Qa-2 isoforms, and to perform crystallography on the highly
     purified Qa-2 proteins in order to solve a 3D structure of the
     nonclassical MHC antigen.

The studies proposed in Aims 1 and 2 will advance the understanding of
the general mechanisms of inducible alternative splicing of eukaryotic
genes and will provide information on specific conditions and cell
subsets during immune responses that correlate with preferential
production of soluble or GPI-linked Qa-2 products.  These data may allow
us to define the physiological functions of the Qa-2 isoforms.  Studies
in Aim 3 will examine directly the peptides bound to these proteins and
will assess structural similarity of Qa-2 polypeptides to classical
transplantation antigens.  The results will be used to deduce the
antigens presented by Qa-2 molecules and the parameters required for
binding of protein fragments by MHC molecules.

In the long term the proposed research may help to design vaccines,
prevent autoimmunity and...

## Key facts

- **NIH application ID:** 3128956
- **Project number:** 2R01AI019624-12
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **SAM.gov UEI:** YZJ6DKPM4W63
- **Principal Investigator:** IWONA T STROYNOWSKI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $222,902
- **Award type:** 2
- **Project period:** 1992-06-01 → 1998-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3128956

## Citation

> US National Institutes of Health, RePORTER application 3128956, TRANSPLANTATION ANTIGENS--EXPRESSION AND FUNCTION (2R01AI019624-12). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3128956. Licensed CC0.

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