A number of T-cell membrane molecules influence the outcome of antigen recognition by TCR/CD3 complex. CD4, by virtue of its non-covalent association with the protein tyrosine kinase lck has the capacity to enhance TCR$ alpha beta$ signalling. The extracellular domain of CD4 interacts with monomorphic determinants of Major Histocompatibility complex class-II molecules such that antigen presented in association with MHC class-II to CD4$ sp+$ T-cells results in the coaggregation of CD4 and TCR/CD3, thus juxtaposing lck and the antigen-receptor complex. Anti-CD4 antibodies abrogate both antigen and anti-TCR-induced T-cell activation. Studies using antigen specific T-cell clones that express either no CD4, wild type CD4 or mutated CD4 that cannot associate with lck (Db CYS) indicate that CD4 sequesters the majority of cellular lck and when not coaggregated with TCR/CD3, prevents the generation of prerequisite signals. / Results presented in this thesis indicate that while CD4-associated lck is providing prerequisite signals for TCR/CD3 signalling, the contribution of CD4 must be more than simply providing a shuttle for lck. Specifically, anti-CD4 inhibits the antigen response of Db CYS CD4-expressing clones. This result cannot be accounted for either by CD4 sequestration of lck, or reduction of avidity of the interaction between the T-cell and the antigen presenting cell, since CD4$ sp-$ variants exhibit an antigen response comparable to that of CD4$ sp+$ variants. Rather, they suggest a novel role for the ectodomain of CD4 in antigen-induced T-cell activation.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.68156 |
| Date | January 1993 |
| Creators | Bonnard, Madeleine |
| Contributors | Julius, Michael (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Microbiology and Immunology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001397512, proquestno: AAIMM94413, Theses scanned by UMI/ProQuest. |
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