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.
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