{"id":{"repo_id":"mit","oai_identifier":"oai:dspace.mit.edu:1721.1/8383"},"canonical_url":"https://search.dev.ndltd.org/etd/mit/oai:dspace.mit.edu:1721.1/8383","repository":{"repo_id":"mit","name":"MIT","base_url":"https://dspace.mit.edu/oai/request"},"display":{"title":"The role of nonclassical MHC class I products in the development and function of CD8+ T cells","abstract":"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.","abstract_html":"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.","abstract_has_math":false,"creators":["Halme, Dina Gould, 1974-"],"institution":"Massachusetts Institute of Technology","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":"Massachusetts Institute of Technology. Dept. of Biology.","school":null,"contributors":[],"advisors":["Hidde L. Ploegh."],"committee_chairs":[],"committee_members":[],"year":2002,"date_issued":"2002","date_published":"2002","updated_at":"2026-07-22T22:21:36Z","subjects":["Biology."],"languages":["eng"],"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."],"rights_urls":["http://dspace.mit.edu/handle/1721.1/7582"],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/1721.1/8383","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Hidde L. Ploegh."]},{"key":"dc:contributor.department","label":"Department","values":["Massachusetts Institute of Technology. Dept. of Biology."]},{"key":"dc:contributor.other","label":"Dc Contributor Other","values":["Massachusetts Institute of Technology. Dept. of Biology."]},{"key":"dc:creator","label":"Author","values":["Halme, Dina Gould, 1974-"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2005-08-23T19:43:38Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2005-08-23T19:43:38Z"]},{"key":"dc:date.issued","label":"Date","values":["2002"]},{"key":"dc:publisher","label":"Institution","values":["Massachusetts Institute of Technology"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Biology."]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["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."]},{"key":"dc:rights.uri","label":"Rights URI","values":["http://dspace.mit.edu/handle/1721.1/7582"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/1721.1/8383"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Biology, June 2002.","\"May 2002.\"","Includes bibliographical references."]},{"key":"dc:description.abstract","label":"Abstract","values":["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.","(cont.) The 2C TCR has been described as restricted to the classical class I product Kb. However, we demonstrate that 2C TCR+ T cells can develop in the absence of Kb molecules, but not in 2m-/- mice, and therefore must require a nonclassical class I product for their maturation. These nonclassical class I-dependent 2C T cells are found in fetal thymic organ cultures, neonatal thymi, and the intestine of adult mice. We also demonstrate that CD8+ T cells restricted to nonclassical class I products provide full immunity against secondary lethal infections with Listeria monocytogenes. These nonclassically-restricted T cells expand disproportionately in KbDb-/- mice and are activated by Listeria-derived antigens presented by H-2M3 and CD1d."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Ph.D."]},{"key":"dc:format.mimetype","label":"Dc Format Mimetype","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["The role of nonclassical MHC class I products in the development and function of CD8+ T cells"]}]}],"canonical_facts":{"dc:contributor.advisor":["Hidde L. Ploegh."],"dc:contributor.department":["Massachusetts Institute of Technology. Dept. of Biology."],"dc:contributor.other":["Massachusetts Institute of Technology. Dept. of Biology."],"dc:creator":["Halme, Dina Gould, 1974-"],"dc:date.accessioned":["2005-08-23T19:43:38Z"],"dc:date.available":["2005-08-23T19:43:38Z"],"dc:date.issued":["2002"],"dc:description":["Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Biology, June 2002.","\"May 2002.\"","Includes bibliographical references."],"dc:description.abstract":["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.","(cont.) The 2C TCR has been described as restricted to the classical class I product Kb. However, we demonstrate that 2C TCR+ T cells can develop in the absence of Kb molecules, but not in 2m-/- mice, and therefore must require a nonclassical class I product for their maturation. These nonclassical class I-dependent 2C T cells are found in fetal thymic organ cultures, neonatal thymi, and the intestine of adult mice. We also demonstrate that CD8+ T cells restricted to nonclassical class I products provide full immunity against secondary lethal infections with Listeria monocytogenes. These nonclassically-restricted T cells expand disproportionately in KbDb-/- mice and are activated by Listeria-derived antigens presented by H-2M3 and CD1d."],"dc:description.degree":["Ph.D."],"dc:format.mimetype":["application/pdf"],"dc:identifier.uri":["http://hdl.handle.net/1721.1/8383"],"dc:language.iso":["eng"],"dc:publisher":["Massachusetts Institute of Technology"],"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."],"dc:rights.uri":["http://dspace.mit.edu/handle/1721.1/7582"],"dc:subject":["Biology."],"dc:title":["The role of nonclassical MHC class I products in the development and function of CD8+ T cells"],"dc:type":["Thesis"]},"updated_at":"2026-07-22T22:21:36Z"}