# NON-H-2 HISTOCOMPATIBILITY GENES AND ENCODED ANTIGENS

> **NIH NIH R01** · MC LAUGHLIN RESEARCH INSTITUTE · 1990 · $156,985

## Abstract

Histocompatibility (H) antigens encoded by genes mapping outside
of the major histocompatibility complex comprise a formidable
barrier to successful tissue transplantation.  Although the family
of non-H-2 H antigens in the mouse has served as an important
model system for studying the regulation of the T cell response,
virtually nothing is known of the origins and functions of these
antigens.  This continuing program has been aimed at elucidating
the mechanisms of responses to multiple and single H antigens.
We have recently discovered that H antigens are generated by
germline integration of retroviruses and tumor viruses.  The
proposed research plan is a multi-faceted approach to
understanding the mechanisms and regulation of the T cell
response to H antigens and the identification of members of this
important family.  The first experiments are aimed at revealing
the basis for the preferential, in vitro T cell response to
immunodominant antigens and its relevance to T cell responses in
vivo.  Potential roles for (1) preferential presentation of dominant
antigens by H-2K/D molecules, (2) differences in affinity and
number of IL-2 receptors on T cells specific for dominant and
dominated antigens, and (2) different classes of dominant antigens
for helper and cytolytic T cells will be investigated.  The T cell
response to single H antigens will be analyzed to determine (1) the
role of discrete regions of H-2K molecules in H antigen
presentation and determination of Ir gene status, (2) the effects
of T cell receptor V genes used by H antigen-specific T cells on
antigen specificity and H-2 restriction, and (3) the relationship
between the mechanisms of in vivo and in vitro T cell responses.
These studies will be complemented by the cloning and
identification of non-H-2 H genes.  The observation that the SV40
T-antigen is seen as an H antigen in transgenic mice will be
extended by determining the effects of different promoters and
flanking regions on its expression as an H antigen.  The
association between a new mammary tumor virus and a mutant H
antigen will be confirmed by cloning this retrovirus to assess its
ability to encode this H antigen.  The relationship between coat
color and H gene mutations will be extended to confirm that coat
color mutant reversions lead to the loss of H antigens.  Finally,
retroviral vectors will be employed as insertional mutagens to
inactivate a single H gene; the cloning of the integrated
retrovirus will facilitate the first cloning of an H gene from a
cosmid library.

## Key facts

- **NIH application ID:** 3126539
- **Project number:** 5R01AI016052-14
- **Recipient organization:** MC LAUGHLIN RESEARCH INSTITUTE
- **SAM.gov UEI:** HFVPWLV7WAJ3
- **Principal Investigator:** Peter Johnson Wettstein
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $156,985
- **Award type:** 5
- **Project period:** 1989-12-01 → 1991-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3126539

## Citation

> US National Institutes of Health, RePORTER application 3126539, NON-H-2 HISTOCOMPATIBILITY GENES AND ENCODED ANTIGENS (5R01AI016052-14). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3126539. Licensed CC0.

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