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Analysis of antigen handling by epidermal Langerhans' cells during the early neonatal period

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Bellette, Bernadette M.(Bernadette Mary) (2004) Analysis of antigen handling by epidermal Langerhans' cells during the early neonatal period. PhD thesis, University of Tasmania.

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Abstract

Antigen applied to the epidermis of 4-day-old mice results in antigen specific
immune suppression and is linked to a decrease in the amount of antigen transported
to the draining lymph node by epidermal Langerhans cells (LC). It was therefore
proposed that a decrease in receptor-mediated endocytosis was responsible for the
reduced antigen transport by the LC. Consequently the aims of this study were to
characterise the expression of antigen uptake receptors during development of
neonatal mice, evaluate their capacity to internalise antigens via receptor-mediated
and fluid phase uptake and to assess antigen proteolysis and MHC-II complexing
following exposure to maturation stimuli.
Langerhans cells isolated from 4-day-old epidermis express reduced levels of the Ctype
lectin receptors DEC-205 and Langerin in comparison to LC isolated from 6-
week-old epidermis. Despite this reduction neonatal LC were efficient in the uptake
of the mannosylated antigen FITC-dextran. When incubated in the presence of the
macropinocytosis inhibitor wortmannin, antigen uptake was reduced to a greater
extent in neonatal LC than adult counterparts. As such, neonatal LC preferentially
utilise a wortmannin-sensitive fluid phase pathway, such as macropinocytosis, to
internalise antigens such as FITC-dextran. Despite the presence of LAMP-1 +MHC-II+ vesicles within LC from neonatal
epidermis, proteolysed DQ-OVA was localised to a MHC-II" compartment. This
suggests that antigen was internalised via macropinocytosis and retained in a LAMPmacropinosome.
As no differences were observed in DQ-OVA+ vesicle
localisation, it was evident that neonatal and adult LC were associated with a
comparable proteolytic activity. 24 hours following exposure to a maturationinducing
dose of LPS, membrane MHC-II:peptide complexes were evident on adult
LC, but not on neonatal LC. Although neonatal LC demonstrated both CD86 upregulation
and MHC-II redistribution following LPS exposure, the transport of
MHC-II:peptide complexes to the membrane was diminished. This reduced transport
was not simply due to a defect in MHC-II recycling as LPS stimulation of LC caused
a redistribution of MHC-II from an intracellular endosome to the cell surface. Therefore the reduced transport of MHC-II:peptide to the cell surface was most
likely a consequence of a failure to associate with MHC-II in the cytoplasm.
The capacity of neonatal LC to sample their external environment without inducing
immunity has important biological consequences for the protection against
inappropriate responses during the developmental period.

Item Type: Thesis (PhD)
Keywords: T cells, Immunosuppression, Langerhans cells, Antigens
Copyright Holders: The Author
Copyright Information:

Copyright 2004 the Author - The University is continuing to endeavour to trace the copyright
owner(s) and in the meantime this item has been reproduced here in good faith. We
would be pleased to hear from the copyright owner(s).

Additional Information:

Thesis (Ph.D.)--University of Tasmania, 2005. Includes bibliographical references

Date Deposited: 25 Nov 2014 00:54
Last Modified: 08 Jun 2016 03:36
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