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The molecular mechanisms of accessory cell-T lymphocyte interaction

King, P. D.; (1992) The molecular mechanisms of accessory cell-T lymphocyte interaction. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

By a process of negative selection, lymphoid dendritic cells were isolated to high purity from human tonsils. In comparison with other purified tonsillar accessory cell types these dendritic cells were shown to be potent inducers of T lymphocyte proliferation in the periodate oxidative mitogenesis reaction, autologous MLR and allogeneic MLR. The tonsillar dendritic cell induced oxidative mitogenesis reaction was used as a model to study the molecular mechanisms of dendritic cell induced T lymphocyte proliferation. For this, panels of antibodies were used as tools to probe different aspects of the cell-cell interaction. The results indicate that dendritic cells induce T lymphocyte proliferation by a complex two stage mechanism. One stage is an early dendritic cell-T lymphocyte clustering stage which is mediated by LFA-1, ICAM-1, the CD2 antigen and LFA-3 and in which the CD45 antigen plays an indirect role. The other stage is a signal transduction stage. LFA-1, ICAM-1, the CD2 antigen, LFA-3 and the CD45 antigen are also implicated at this stage in addition to a variety of other molecules including the CD3, CD4, CDS, CD25, CD26, CD28, CD39, CD44, CD48, CDw70, CD71 and CDw78 antigens and class I and II MHC. In quantitative assays the molecular events involved in PMA differentiated U937-T lymphocyte clustering were also investigated. This type of clustering is mediated by the same epitopes of LFA-1 and ICAM-1 as dendritic cell-T lymphocyte clustering and again the CD45 antigen is indirectly implicated. There are differences, however, in that the CD2 antigen and LFA-3 are not involved and that the CD44 antigen and class II MHC, too, play an indirect role. Along with evidence that the roles of the CD44 and CD45 antigens in U937-T clustering are distinct, these findings emphasise the heterogeneity of structures and mechanisms involved in accessory cell-T lymphocyte interaction.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: The molecular mechanisms of accessory cell-T lymphocyte interaction
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Health and environmental sciences; Dendritic cells
URI: https://discovery.ucl.ac.uk/id/eprint/10114202
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