# NON-H-2 HISTOCOMPATIBILITY GENES AND ENCODED ANTIGENS

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 1993 · $269,624

## Abstract

The success or failure of tissue allografts is determined by the products
of a large family of autosomal and sex-linked, polymorphic genes that are
designated histocompatibility (H) genes.  The strongest barriers to
successful transplantation are determined by the alloantigenic products of
class I and class II genes of the major histocompatibility complex (MHC).
The matching of donors and recipients for MHC class I and class II
alloantigens not only reduces or eliminates MHC-encoded barriers but,
conversely, optimizes the presentation of donor minor H antigens that
require MHC matching of donor and recipient for presentation.  The
demonstration that the antigenic components of single minor H antigens are
peptides bound to the peptide binding site of MHC molecules provides not
only a reason for why minor H genes have eluded cloning, but, also provides
an experimental approach to identifying and sequencing these H antigen
peptides.  Using the knowledge of the class I molecule that is required for
the presentation of a single minor H antigen to cytolytic T lymphocytes
(CTL) and the fact that subsets of endogenous peptides bind to individual
class I molecules, we have chromatographically resolved peptides from
multiple minor H antigens.  The amino acid sequences of these minor H
peptides can be applied to cloning and sequencing the respective genes.
The overall objectives of this research program are to clone and identify
minor H genes in the mouse and to understand the specificity and genetic
control of the T cell response to their encoded antigens.  The first aim is
the amino acid sequencing of minor H antigen peptides by mass spectrometry
and application of the amino acid sequences to the synthesis of degenerate
oligonucleotides for the cloning of minor H gene CDNAS.  H gene CDNAS will
be confirmed by sequencing and DNA-mediated gene transfer into eukaryotic
cells with subsequent testing with specific CTL.  The second objective is
the estimation of diversity of minor H peptides expressed by inbred mouse
strains by amplification and sequencing of DNA sequences that encode the
homologous peptides.  The third objective is the testing of our hypothesis
that minor H peptides comprise a group of non-abundant endogenous peptides
that exhibit relatively higher affinity for class I molecules than that
exhibited by abundant, endogenous peptides.  Peptides derived from minor H
antigens, viral and soluble antigens, and abundant endogenous proteins will
be tested for relative affinity in competitive binding assays and assays
for stabilization of expression of class I:peptide complexes.  The fourth
objective is the sequencing of immunodominant minor H antigen peptides and
the testing of the hypothesis that the ranking of these dominant antigens
is based on the relative affinity of their peptides for class I molecules.
These studies constitute the first analysis of the T cell response to minor
H antigens that will both sequence minor H antigen peptides and genes...

## Key facts

- **NIH application ID:** 3126534
- **Project number:** 2R01AI016052-17
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **SAM.gov UEI:** Y2K4F9RPRRG7
- **Principal Investigator:** Peter Johnson Wettstein
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $269,624
- **Award type:** 2
- **Project period:** 1989-12-01 → 1998-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3126534

## Citation

> US National Institutes of Health, RePORTER application 3126534, NON-H-2 HISTOCOMPATIBILITY GENES AND ENCODED ANTIGENS (2R01AI016052-17). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3126534. Licensed CC0.

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