ANALYSIS OF MHC-ENCODED CELL SURFACE ALLOANTIGENS

  • Wettstein, Peter J, (PI)

Project: Research project

Project Details

Description

The major histocompatibility complex (MHC) of mammals plays a pivotal role
in antigen-specific regulation of the immune response of thymus-derived (T)
lymphocytes. In fact, the MHC has been implicated in regulating
susceptibility to a variety of disease states including diabetes melitus
and multiple sclerosis. Therefore, the critical evaluation of the
organization and structure of Class I and Class II MHC genes and the
immunological function of their cell-surface products is of paramount
importance. The laboratory rat has provided an excellent model for a
number of human disease states; this fact emphasizes the urgency for a
comprehensive, genetic and functional analysis of the rat MHC, RT1. The
research program proposed in this application comprises such a
comprehensive analysis. The primary objective of this program is the
cloning of individual RT1 Class I and Class II genes followed by the
characterization of their gene products at the molecular and functional
levels in isolation in mouse cells after DNA-mediated gene transfer. The
minimum number and polymorphism of RT1 Class I and Class II sequences will
be obtained with genomic blots of digested DNA derived from a panel of
inbred strains, intra-RT1 recombinant strains, wild rat-derived congenic
strains, and captured wild rats. Class I and Class II sequences will be
cloned from Lambda genomic libraries; cloned genes will be characterized by
(1) restriction site mapping, (2) nucleotide sequencing, and (3) intra-RT1
mapping. Cloned Class I and Class II sequences will be transferred to
mouse tissue culture cells by DNA-mediated gene transfer; expressed RT1
gene products will be characterized by serology, two-dimensional gel
electrophoresis, and T cell- mediated assays. The ability of Class I and
Class II gene products to present foreign antigens to cytotoxic and
IL-2-secreting T cells, respectively, will be investigated. Specifically,
Class II gene products will be tested, in collaboration, for their ability
to present myelin basic protein to rat IL-2-secreting T cells with the aim
of identifying the functional Class II gene(s) and the domain of its
product involved in presentation of antigen in the experimental allergic
encephalitis syndrome. The proposed experiments are expected to assign
specific molecular characteristics and immunological functions of RT1 genes
to individual genes.
StatusFinished
Effective start/end date4/1/823/31/90

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

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

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