Studies of Non-Classical Antigen Presentation Molecules: Functional Analysis of Mouse Qa-1 and Characterization of the Porcine CD1 Gene Family

"""Nonclassical"" major histocompatibility complex (MHC) class I-b molecules are structurally homologous with ""classical"" MHC class I-a molecules. Some MHC class I-b molecules appear to have a specialized antign (Ag) presentation role in given species. Two MHC class I-b molecules were studied, mouse Qa-1 and porcine CD1. First, Qa-1 expression was examined in pancreatic β-cells. The demonstration of interferon-γ-regulated Qa-1$\rm\sp{b}$ expression in β-cells along with the identification of a putative Qa-1$\rm\sp{b}$ peptide (Ins II; ALWMRFLPL) in the insulin leader sequence indicates that Qa-1 expression by pancreatic β-cells may play a role in the progression of islet inflammation. Further, the lack of Qa-1$\rm\sp{a}$ on NIT-1 cells, pancreatic β-cells derived from NOD mice, forces consideration of the role of Qa-1 in immune regulation. In a second set of experiments, one porcine CD1 gene (pCD1.1) was isolated and characterized at the molecular and cellular level. The CD1 family of Ag presentation molecules seems to be adapted primarily for the presentation of nonpeptide Ags such as glycolipids and lipids. The number and structural diversity of CD1 loci among mammalian species may indicate rapid evolution of this gene family. The porcine pCD1.1 cDNA sequence contained an open reading frame of 1020 base pairs encoding 339 amino acids. In contrast to the α3 domain, the α1 and α2 domains of pCD1.1 exhibit marked amino acid dissimilarities compared to other CD1 molecules. However, pCD1.1 contains well conserved N-linked glycosylation sites within α1 and α2 domains of ""classical"" CD1 molecules. Also, distinct from other CD1 molecules, pCD1.1 has a unique cytoplasmic tail composed of fourteen amino acids, containing a possible motif (D-P-S-S) which resembles conserved serine phosporylation motifs (D/E-X-S-L; X, any amino acids) within MHC class I-a cytoplasmic tails. Phylogenetic analysis of CD1 molecules among mammalian species revealed that pCD1.1 is most closely related to human CD1A. Emergence of pCD1.1 was earlier than CD1E and later than CD1C, based on branching order. Porcine pCD1.1 mRNA was expressed in CD3$\sp-$ thymocytes and professional antigen presenting cells (APCs). Together, the unique structure and expression of pCD1.1, combined with phylogenetic analysis, places pCD1.1 on a new branch of the classical CD1 family."

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Animal Sciences

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Chun, Taehoon

Contributors dc:contributor

• Gaskins, H. Rex

• Biology, Molecular

Language dc:language

eng

Identifier

(MiAaPQ)AAI9904411

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/83641