IBD AND THE MHC--MODEL STUDIES

Project: Research project

Description

DESCRIPTION: The New World
primate Saguinus oedipus (the cotton-top tamarin) suffers from an
extremely high incidence of ulcerative colitis and adenocarcinoma of the
colon and is unusually susceptible to lethal infection with a variety
of viruses. Tamarins are unusual in that their cells express HLA-G-
related MHC class I molecules with limited polymorphism and variability.
An elucidation of the ramifications of the expression of these HLA-G-
related MHC class I molecules should lead to important advances in our
understanding of the functional characteristics of the tamarins' immune
system and may, thus, provide an explanation for the extraordinary
incidence of colitis and adenocarcinoma of the colon in the tamarin. A
possible relationship between MHC haplotype and susceptibility to
disease is becoming increasingly evident. Peptide transporter,
proteosome, tumor necrosis factor and the complement genes are also
located in the MHC.Tamarins have deleted the homologues of the HLA-A, -
B and -C loci. If some of these other MHC genes were deleted along with
these HLA-1, -B and -C homologues, this might render the tamarin
sensitive to a variety of pathological processes. It has been shown that
certain disease susceptibilities, including susceptibility to several
gastrointestinal diseases, can be linked to certain MHC haplotypes.
Therefore, this application proposes to determine whether there is a
relationship between MHC haplotype and the extraordinary incidence of
ulcerative colitis and adenocarcinoma of the colon in the tamarin.
Specific Aim 1 proposes to assess the role played of tamarins' non-
polymorphic, non-variable, HLA-G-related MHC class I molecules in the
tamarins' immune response to pathogens.Specific Aim 2 proposes to define
the extent of the deletion that led to the loss of the homologues of
HLA-1, -B and -C in the tamarin. Specific Aim 3 proposes to determine
whether susceptibility to adenocarcinoma of the colon is linked to MHC
haplotype in the tamarin.
StatusFinished
Effective start/end date9/15/948/31/99

Funding

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

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HLA-G Antigens
Haplotypes
Adenocarcinoma
HLA-B Antigens
Colon
Disease Susceptibility
Colitis
Saguinus
Ulcerative Colitis
Incidence
HLA-A Antigens
Pathologic Processes
Genes
Tumor Necrosis Factor-alpha
Viruses
Gastrointestinal Diseases
Infection
Primates
Immune System

ASJC

  • Medicine(all)