The role of nonclassical MHC class I products in the development and function of CD8+ T cells

Major histocompatibility complex (MHC) class I products present pathogen-derived peptides to CD8+ cytotoxic T cells. This interaction mediates the detection and clearance of intracellular infections. Emphasis has been placed on the critical role of classical class I MHC products in the development and function of CD8+ T cells. In this thesis, I demonstrate that nonclassical class I products also play an important role in the development and function of CD8+ T cells. Experiments using TAP1-/- or β2m-/- mice do not distinguish between the involvement of classical and nonclassical class I products. KbDb-/- mice are deficient in the expression of classical class I products but continue to express nonclassical class I products, providing a unique opportunity to examine the relative contributions of these types of molecules to immunity. Although the majority of CD8+ T cells found in the periphery and female reproductive tract are dependent on classical class I for their development, a small but significant population of CD8+ T cells are found in these tissues in the absence of classical class I products. These CD8+ T cells, which mature in KbDb-/- but not β2m-/- mice, are therefore dependent on the expression of nonclassical class I products for their maturation. In contrast, the majority of CD8cαα+ TCRαβ intestinal intraepithelial lymphocytes (iIELs) develop independently of classical class I expression and are dependent on the nonclassical class I product Qa-2 for their maturation.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Biology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2002

Author dc:creator

• Halme, Dina Gould, 1974-

Advisor dc:contributor.advisor

• Hidde L. Ploegh.

• Biology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/8383

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/8383