Date of Award:

12-2013

Document Type:

Dissertation

Degree Name:

Doctor of Philosophy (PhD)

Department:

Animal, Dairy, and Veterinary Sciences

Committee Chair(s)

Christopher Davies

Committee

Christopher Davies

Committee

Gregory J. Podgorski

Committee

Kenneth L. White

Committee

Lee F. Rickords

Committee

Thomas D. Bunch

Committee

Dirk K. Vanderwall

Abstract

This project was funded by the United States of Department of Agriculture (USDA), which funds research aimed at improving production and animal health. The aim of this study was to advance knowledge of maternal immune tolerance to the fetus and mechanisms bovine non-classical MHC class I proteins employ to interact with immune cells and render them inert towards the fetus.

A fetus is a tissue graft inside the mother’s uterus yet must be accepted by the mother to maintain a successful pregnancy. Reproductive insufficiency and pregnancy failure are major causes of production loss in cattle, especially in cloned animals. Knowledge of the receptors that non-classical MHC class I proteins interact with may make it possible to improve reproductive efficiency in cattle. We have shown that three non-classical MHC class I proteins expressed during the third trimester, NC1*00501, NC3*00101, and NC4*00201, are expressed as cell-surface isoforms. The other non-classical class I proteins, that we studied, NC1*00401 and NC2*00102, were not expressed on the surface of our cell lines and may be secreted or soluble proteins. The non-classical class I proteins expressed and/or secreted by embryos at different gestational stages can be detected using enzyme-linked immunosorbent assays (ELISA). We were able to produce a NC3*00101-specific monoclonal antibody for use in ELISA; however, we lost the cell line when we attempted to clone it.

Understanding the patterns of expression of these proteins during different stages of pregnancy will help elucidate the association of these proteins with pregnancy success in normal and cloned cattle and will provide insights into mechanisms that prevent rejection of the fetus by the potentially hostile maternal immune system. To elucidate how non-classical class I proteins interact with white blood cells in the uterus, we initiated studies to identify NC3*00101-specific peptide ligands needed to make NC3*00101 tetramers, which can be used to understand interactions between MHC molecules and white blood cells. Understanding the interactions of non-classical class I proteins with maternal immune cells will reveal the mechanisms of inhibitory action that are used by class Ib proteins to suppress the maternal immune system and protect the fetus.

This study helped to elucidate patterns of expression of cattle non-classical MHC class I proteins, which are important to maintain a favorable environment within uterus during pregnancy.

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