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Recombinant antibodies which deliver T cell epitopes of gliadin peptides
causitive of celiac disease to antigen-presenting cells in the thymus might
be used to induce deletion of the thymocytes (immature T cells) involved in
celiac disease pathogenesis, preventing or ameliorating celiac disease.
Experiments which inject such antibodies into mice show promise.

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Eur J Immunol. 2005 Sep 23; [Epub ahead of print]

Induction of central T cell tolerance: Recombinant antibodies deliver
peptides for deletion of antigen-specific CD4(+)8(+) thymocytes.

Schjetne KW, Thommesen JE, Fredriksen AB, Lunde E, Sandlie I, Bogen B.

Institute of Immunology, University of Oslo and Rikshospitalet University
Hospital, Oslo, Norway.

In order to prevent or ameliorate autoimmune disease, it would be desirable
to induce central tolerance to peripheral self-antigens. We have
investigated whether recombinant antibodies (Ab) that deliver T cell
epitopes to antigen-presenting cells (APC) in the thymus can be used to
induce thymocyte deletion. Troybodies are recombinant Ab with V regions
specific for APC surface molecules that have T cell epitopes genetically
introduced in their C domains. When MHC class II-specific Troybodies with
the lambda2(315 )T cell epitope were injected into lambda2(315)-specific
TCR transgenic mice, a profound deletion of CD4(+)8(+) thymocytes was
observed. MHC class II-specific Troybodies were 10-100-fold more efficient
than non-targeting peptide Ab, and 500-fold more efficient than synthetic
peptide at inducing deletion. Similar findings were observed when MHC class
II-specific Troybodies with the OVA(323-339) T cell epitope were injected
into OVA-specific TCR transgenic mice. Although deletion was transient
after a single injection, newborn mice repeatedly injected with MHC class
II-specific Troybodies for 4 weeks, had reduced antigen-specific T cells in
peripheral lymphoid tissues and reduced T cell responses. These experiments
suggest that Troybodies constructed to target specifically thymic APC could
be useful tools for induction and maintenance of central T cell tolerance
in autoimmune diseases.

PMID: 16184515 [PubMed - as supplied by publisher]

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