# IMMUNOGENETICS OF HYBRID RESISTANCE

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 1990 · $220,252

## Abstract

The long-term goal is to determine the genetic mechanism of expression of
Hemopoietic histocompatibility (Hh) antigens on the surface of leukemic and
normal progenitor cells and characterize the Hh molecules themselves.  To
that end the following Aims are described:  1. Confirm the conclusion that
Hh antigenic expression on lymphoma cells is "down-regulated" by
trans-acting regulatory genes.  Using both in vivo and in vitro assays for
hybrid resistance in which "cold target cells competition" can be measured,
we observed that ACCb H-2d/H-2b loss mutants which had lost Dd gained the
expression of Hhb.  2. Map the Hh genes more precisely.  B10.RQDB is a new
H-2 recombinant described by Chella David, which expresses Dd, Db, but not
Ld.  Therefore, recombination occurred between D and L and Db is really
Lb.  The marrow cells have lost Hhb, retained Hhd for allogenic hosts and
have decreased Hhd for F1 hybrid hosts.  There and other new recombinants
will be used to map Hh, which should be contromeric to L since the sequence
is D (R) L in the D-region.  (3) Test the cis gene hypothesis, i.e. an
adjacent gene regulates Hh expression.  Use same new H-2 recombination to
detect gene(s) between S and L which may regulate Hh expression in
heterozygotes that regulated "tolerance" to parental Hh antigen.  (4)
Continue to test the "allogenic inhibition" hypothesis for hybrid
resistance.  Marrow cells from C.B-17 scid/scid donors, which cannot
generate alloreactive T or B cells, nevertheless are rejected by irradiated
allogeneic or F1 hybrid recipient mice.  (5) Characterize Hh molecules.
2-D gels of lysates of 35S-methionine labeled EL-4 and various ACCb cell
lines, followed by computer analysis of radiographs, identified a 90 kd
molecule as a potential candidate for the Hhb antigen.  We will generate
antibodies to isolate the molecules, and study its structure.

## Key facts

- **NIH application ID:** 3174574
- **Project number:** 2R01CA036921-07
- **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:** 1990
- **Award amount:** $220,252
- **Award type:** 2
- **Project period:** 1984-03-01 → 1993-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3174574

## Citation

> US National Institutes of Health, RePORTER application 3174574, IMMUNOGENETICS OF HYBRID RESISTANCE (2R01CA036921-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3174574. Licensed CC0.

---

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