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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK044886-04
Application #
2518318
Study Section
Immunobiology Study Section (IMB)
Program Officer
Hamilton, Frank A
Project Start
1994-09-15
Project End
1999-08-31
Budget Start
1997-09-01
Budget End
1999-08-31
Support Year
4
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Veterinary Sciences
Type
Other Domestic Higher Education
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Cadavid, L F; Mejia, B E; Watkins, D I (1999) MHC class I genes in a New World primate, the cotton-top tamarin (Saguinus oedipus), have evolved by an active process of loci turnover. Immunogenetics 49:196-205
Evans, D T; Knapp, L A; Jing, P et al. (1999) Three different MHC class I molecules bind the same CTL epitope of the influenza virus in a primate species with limited MHC class I diversity. J Immunol 162:3970-7
Knapp, L A; Cadavid, L F; Watkins, D I (1998) The MHC-E locus is the most well conserved of all known primate class I histocompatibility genes. J Immunol 160:189-96
Evans, D T; Piekarczyk, M S; Cadavid, L et al. (1998) Two different primate species express an identical functional MHC class I allele. Immunogenetics 47:206-11
Evans, D T; Piekarczyk, M S; Allen, T M et al. (1997) Immunodominance of a single CTL epitope in a primate species with limited MHC class I polymorphism. J Immunol 159:1374-82
Cadavid, L F; Shufflebotham, C; Ruiz, F J et al. (1997) Evolutionary instability of the major histocompatibility complex class I loci in New World primates. Proc Natl Acad Sci U S A 94:14536-41
Cadavid, L F; Watkins, D I (1997) The duplicative nature of the MHC class I genes: an evolutionary perspective. Eur J Immunogenet 24:313-22
Cadavid, L F; Watkins, D I (1997) Heirs of the jaguar and the anaconda: HLA, conquest and disease in the indigenous populations of the Americas. Tissue Antigens 50:209-18
Cadavid, L F; Watkins, D I (1997) Heirs of the jaguar and the anaconda: HLA, conquest and disease in the indigenous populations of the Americas. Tissue Antigens 50:702-11
Cadavid, L F; Hughes, A L; Watkins, D I (1996) MHC class I-processed pseudogenes in New World primates provide evidence for rapid turnover of MHC class I genes. J Immunol 157:2403-9

Showing the most recent 10 out of 11 publications