Recombinant antibodies with the antigen-specific, MHC restricted specificity of T cells: novel reagents for basic and clinical investigations and immunotherapy.

MHC class I and II molecules play a central role in the immune response against a variety of invading microorganisms and cells that have undergone malignant transformation by shaping the T cell repertoire in the thymus and by presenting peptide antigens from endogenous and exogenous antigens in the periphery to CD8+ cytotoxic T cells and CD4+ helper T cells. In certain situations MHC-peptide complexes may, however, also initiate and perpetuate an autoimmune attack mediated by autoaggressive T cells leading to diseases such as insulin dependent diabetes mellitus (IDDM), rheumatoid arthritis (RA) and multiple sclerosis (MS). Such MHC-peptide complexes are a desirable target for novel approaches in immunotherapy. Targeted delivery of toxins or other cytotoxic drugs to cells which express specific MHC-peptide complexes that are involved in the immune response against cancer or viral infections and specific masking of MHC-peptide complexes that are involved in autoimmune reactions would allow for a specific immunotherapeutic treatment of these diseases. We have recently demonstrated that antibodies with the antigen-specific, MHC restricted specificity of T cells can be readily generated by taking advantage of the selection power of phage display technology.