Abstracts (complete list) - Wissenschaft Online

Sabine Höpner, Katharina Dickhaut, Jamina Eckhard, Shashank Gupta, Kirsten Falk,
Olaf Rötzschke
Amplification of CD4 T cell responses by catalysing antigenloading
through MHC-loading Enhancer (MLE)
In previous studies we identified a set of small molecular compounds which have the
capacity to enhance loading of peptides/proteins onto MHCII molecules. We showed the
enhancement of antigen-loading on soluble as well as membrane bound MHCII-
Molecule. In particular adamantanethanole (AdEtOH) strongly accelerates the antigenloading
rate. This effect is obvious for HLA-DR molecules expressing Glycine at position
beta 86 of the pocket P1, which is located in the binding site. The dimorphic position
(Glycine/Valine) determines the depth of the conserved pocket P1 in the MHC-molecule.
MLEs transiently occupies the P1 and stabilizing the receptive conformation, which leads
to rapid ligand exchange.
We are able to show the correlation between the depth of the pocket P1 and allelespecificity.
Additionally there is evidence for using allele-specific compounds, like
AdEtOH as molecular tools for amplifying immune reactions in vivo.
In mouse models we could obtain strongly enhanced specific CD4+- T-cell response
against tumour associated antigens (TAA) by using MLE as vaccine additive
(“adjuvant”). However the observation of rapid ligand exchange from outside by MLEs
could be a risk factor for allergy or autoimmune diseases and gives rise to investigate
environmental factors, which acts by the mechanism of MLEs. Preliminary data show
modulation of autoimmune reaction in EAE-models using AdEtOH. So far, it is important
to investigate the role of MLE in tumour vaccination as well as autoimmunity functions
of small molecular compounds.