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Investigation of the role of atypical chemokine receptors CCRL1 and CCRL2 in antibody aesponses and the battle of the CARs: CD28 costimulatory endodomains endow T Cells with more robust effector functions in vitro compared to their 4-1BB counterparts

Wiggins, Benjamin George (2014)
M.Res. thesis, University of Birmingham.

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Abstract

Project 1:
CC-Chemokine receptor-like 1 (CCRL1) and 2 (CCRL2) are members of the atypical chemokine receptor family. Little is known about the role of these receptors in the antibody response. Mice doubly deficient in CCRL1 and CCRL2 showed no abnormalities in cell localisation in the spleen or lymph nodes and no difference in antibody titres following thymus-dependent (TD) immunisation. However, IgM and IgG3 titres were increased in the thymus-independent 2 response. In the spleen, B cell numbers were increased at rest, but normal after TD immunisation; while in lymph nodes B cell numbers were decreased both before and after TD immunisation.
Project 2:
Chimeric antigen receptors (CARs) combine MHC-independent antigen recognition with T cell effector functions. Second generation CARs encompass a costimulatory endodomain to enhance T cell activation and survival. So far, it is not known whether CD28-containing CARs or 4-1BB-containing CARs provide T cells with favourable responses. Therefore, we compared these two constructs for the in vitro functional T cell output they provide. CD28-CAR+ T cells produced superior IFN-γ and degranulation responses, but 4-1BB-CAR+ T cells showed a greater resistance to apoptosis. Together, these data suggest the CD28-CAR is favourable, showing greater IFN-γ and cytotoxic responses, despite the greater propensity for apoptosis.

Type of Work:M.Res. thesis.
Supervisor(s):Toellner, K. M.
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Immunity and Infection, Institute of Biomedical Research, MRC Centre for Immune Regulation
Subjects:QP Physiology
R Medicine (General)
Institution:University of Birmingham
ID Code:5256
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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