University of Texas, Southwest Medical Center
Exploring Novel Pathways of Immune Defenses Against Orally Ingested Pathogens: Analysis of Nonclassical Class I MHC Antigens in Mouse Intestines.
Present-day research in immunology is overwhelmingly preoccupied with systemic immune responses
and immune mechanisms that operate in infected hosts after the pathogens have already spread from
their initial site of entry into the circulation. Paradoxically, the total number of immune cells dedicated to
fighting systemic infections is lower than the known number of immune cells associated with various
organs of pathogen entry. This suggests that the most vigorous and decisive host/pathogen immune
interactions take place at the mucosal ports of pathogen-entry, before the systemic infection sets in.
We propose to study early events in immune recognition of pathogens in the gastrointestinal tract of
mice. The main focus of this research will be a subfamily of non-classical major histocompatibility
complex (MHC) class Ib antigens that are structurally similar to classical class Ia MHC
antigen-presenting molecules. The class Ib family members will be characterized in terms of their
gut-specific statement and ability to initiate immune response in gut-localized intraepithelial lymphocytes
(IEL) and /or other intestinal immune cells.
Since class Ib MHC molecules are numerous in all rodents, but not in humans, we hypothesize that
their statement helps to protect the hosts from a plethora of pathogens in the natural habitats of the wild
animals. The delineation of the protective pathways orchestrated by class Ib MHC may help to
understand the evolutionary pathways that led humans to shed most of the class Ib MHC genes and to
become more sensitive to gastrointestinal infections than their rodent vertebrate predecessors.