Grant, Catriona Fraser; (1994) Localization of self antigen: Implications for antigen presentation to T cells. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Self serum proteins are processed and bound to class II MHC molecules on antigen presenting cells (APC), such as macrophages, in vivo. The self protein C5 (the fifth component of complement) is used as a model antigen to investigate whether or not peptides derived from proteins synthesized by macrophages themselves are presented by class II MHC molecules to T cells. Intracellular proteins are not generally presented in the context of class II MHC molecules, although there are exceptions to this described in transfected or virally infected cells. When C5 expression is restricted to macrophages, there is no evidence that this self antigen is presented. The aim of this project was to determine why macrophages do not present their self-synthesized C5 in the context of class II MHC. The possibilities include:- (1) macrophages do not synthesize C5 (2) macrophage synthesized C5 is not immunogenic (3) compartmentalization prevents intracellular C5 peptides from binding to class II (4) extracellular C5 does not reach the required concentration (5) macrophages are not able to activate resting T cells C5(+) macrophages were found to synthesize C5. C5 secreted in vitro by macrophages could be presented by macrophages to a T cell hybrid in vitro, when given exogenously in an appropriate form (captured by specific antibody). C5 immunoprecipitated from macrophage cultures could initiate a C5 specific antibody response in C5(-) mice. In contrast to dendritic cells (DC), macrophages pulsed with C5 were not efficient in priming C5 specific T cells in vivo. Thus although presentation of this self antigen can be demonstrated in vitro, there is no consequence of presentation detected in vivo. This is due to a number of factors, namely: the localization, concentration and form of the antigen; the ability of APC to take up antigen; and the ability of that APC to activate naive T cells.

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