Project: Research project

Project Details


The objective is to define the relationship between diversity of structure
in MHC genes and the function of those genes in the immune system. The
significance of these studies stems from the fact that our understanding of
the role of MHC genes in immune function is largely derived from analyses
based on polymorphisms defined in inbred mice. Since these structurally
relevant polymorphisms influence function of the MHC products, it is of
great interest to define which polymorphisms are relevant to the
diversification of alleles within inbreeding populations and which are
representative of individuals from genetically isolated populations. The
specific aims are: 1) To characterize a unique MHC haplotype by comparison
with two other previously described haplotypes defining features of
haplotype variation that are relevant to MHC function and evolution. 2) To
determine if haplotypes other than H-2b undergo copy event that lead to
diversification of genes encoding antigen presenting products of the class
I and class II regions of the H-2 complex. 3) To define the relative
contributions of spontaneous point mutations and copy mediated mutations in
the diversification and polymorphism of MHC genes. 4) To analyze the
contribution of polymorphic sequences to encoded function. The analyses
will be accomplished by the molecular genetic comparison of cloned genes
among genetically defined mouse strains. Cosmid and phage genomic
libraries of A.CA, B10.M, C57BL/6 and C57BL/10 lines will be analyzed to
isolate homologous class I and class II sequences. Comparative studies
will be based on restriction endonuclease mapping and DNA sequence analyses
of genes derived from each library. Synthetic oligonucleotide probes will
be used to identify specific DNA sequences that are shared by MHC genes
within and among the H-2f and H-2b haplotypes. Direct DNA sequence
analysis of homologous portions of MHC genes will provide estimates of
spontaneous mutation and copy mediated mutation rates. Hybrid genes will
be constructed and introduced into cells in culture to assess function.
Effective start/end date9/1/868/31/91


  • Medicine(all)
  • Immunology and Microbiology(all)