# IMMUNOBIOLOGY OF HYBRID RESISTANCE

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 1991 · $148,421

## Abstract

Hybrid resistance to bone marrow cell (BMC) grafts in mice is mediated by
natural killer (NK) cells which recognize Hemopoietic histocompatibility
(Hh) antigens (Ag) on stem cells.  The major Hh region, Hh-1, maps in the
S/D interval centromeric of TNF of H-2.  Hh-1 are not class I or II Ag, and
NK cells do not rearrange Ig or T cell receptor genes.  Thus, this is an
opportunity to study a novel Ag-receptor interaction in the immune system.
1) BMC allografts often fail in patients with severe combined immune
deficiency (SCID), devoid of T and B but not NK cell functions; 2)
Allogeneic BMC depleted of T cells (T-) to prevent graft versus host
disease often fail to engraft.  3) An assay for typing donors/hosts for
clinical BMC transplants is needed.  We have 4 specific aims.  1.  Analyze
subsets of NK cells which recognize Hh-1 Ag specifically.  a) Transfer
subpopulations of NK cells separated by flow cytometry, using newly
developed anti-NK monoclonal antibodies (mab), to confer specific Hh-1
reactivity to irradiated mice.  b) Generate and evaluate mab to receptors
for Hh-1 Ag. Receptors will be identified by examining conjugates between
NK cells and Hh-1 specific target cells by immunofluorescence.  2.
Determine mechanisms by which T-BMC are sensitive to hybrid resistance and
devise strategies to prevent rejection.  SCID mice will be selectively
repopulated with T cell subsets to identify the cell which prevents hybrid
resistance to their BMC.  3.  Characterize T and NK cells capable of
inhibiting BMC graft rejection.  T cells of radiation chimeras "tolerant"
to Hh-1 Ag will be characterized, and the subsets of NK cells capable of
inhibiting BMC graft rejection will be evaluated.  4.  Develop an vitro
assay for hybrid resistance.  A step-wise approach will involve transfer of
NK cells propagated in IL-2 into hosts; mixing these NK cells with BMC in
vitro before transfer into hosts; finally using an in vitro assay for BMC
viability or function.

## Key facts

- **NIH application ID:** 3174589
- **Project number:** 5R01CA036922-08
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **SAM.gov UEI:** YZJ6DKPM4W63
- **Principal Investigator:** Michael Bennett
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $148,421
- **Award type:** 5
- **Project period:** 1984-03-01 → 1993-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3174589

## Citation

> US National Institutes of Health, RePORTER application 3174589, IMMUNOBIOLOGY OF HYBRID RESISTANCE (5R01CA036922-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3174589. Licensed CC0.

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