Abstract Book 2010 - CIMT Annual Meeting
Abstract Book 2010 - CIMT Annual Meeting
Abstract Book 2010 - CIMT Annual Meeting
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002 Kotsiou | Therapeutic vaccination<br />
Antigen specific monoclonal antibodies directed against the<br />
HA-1 and HA-2 minor histocompatibility antigens<br />
Eleni Kotsiou 1,2 , Jonathan Silk 3 , Vincenzo Cerundolo 3 , Julian Dyson 2 , and Keith G. Gould 1<br />
1<br />
Department of Immunology, Wright-Fleming Institute, St Mary‘s Campus, Imperial College,<br />
London W2 1PG, UK<br />
2<br />
Immunobiology Section, Commonwealth Building, Hammersmith Hospital, Imperial College,<br />
London W12 0NN, UK<br />
3<br />
Tumour Immunology Group, Weatherall Institute of Molecular Medicine, University of Oxford,<br />
Oxford OX3 9DS, UK<br />
38<br />
Monoclonal antibodies with the specificity of a T<br />
cell receptor (TCR) (also known as TCR mimic antibodies)<br />
can be used for the targeting of tumor or<br />
viral epitopes and are potentially very useful in the<br />
clinical setting.<br />
The HA-1 and HA-2 minor histocompatibility (H)<br />
antigens are restricted by human leukocyte antigen<br />
(HLA) A2 and expressed only on normal and malignant<br />
haematopoietic cells. We have produced<br />
soluble (lacking cytoplasmic and transmembrane<br />
regions) HA-1 and HA-2 HLA-A2 single chain<br />
trimers (SCTs) where the peptide, β2-microglobulin<br />
and major histocompatibility complex (MHC) heavy<br />
chain are covalently linked together via glycine/<br />
serine rich linkers. We then used the soluble SCT<br />
proteins to immunize HHD (HLA-A2 transgenic)<br />
mice for the production of antigen specific monoclonal<br />
antibodies by taking advantage of the ‘humanized’<br />
immune system of the transgenic mice<br />
which will recognize the HLA-A2 molecule as ‘self’<br />
but the peptide epitope as foreign.<br />
The screening of the serum of the immunized mice<br />
(after three rounds of immunization) revealed the<br />
presence of antibodies preferentially reacting with<br />
the HA-1 and HA-2 epitopes. The screening of hybridoma<br />
clones produced after fusion of spleen cells<br />
from innunized mice with myeloma cells showed<br />
that, rather than recognising the peptide, the majority<br />
of the monoclonal antibodies were directed<br />
against other immunogenic epitopes present in the<br />
sequence of the HLA-A2 SCTs.<br />
The development of new SCT fusion proteins which<br />
can potentially improve the immunization strategy<br />
will be described.
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