Mark D. Howell

T cell receptors, immunoregulation, and autoimmunity

T cell receptor (TCR) peptide vaccines have proven useful in the prevention and treatment of autoimmune disease in animal models. Prospects for developing TCR peptide vaccines for human autoimmune disease are only now being explored. Preliminary indications provide cause for optimism that immunization with TCR peptides eventually will be a viable treatment option for autoimmune pathologies in humans. In the long term, development of this technology may permit reliable manipulation of T cell immunity, leading to treatments for autoimmunity, T lymphoproliferative disorders, and, in the broadest interpretation, any pathogenesis mediated by oligoclonal T cell populations.

Immunoregulation of Autoimmune Disease by Vaccination with T Cell Receptor Peptides

Restricted TCR gene usage in animal models of autoimmune disease has led to strategies for control of these diseases by targeting the idiotypic determinants within the TCR sequence. Rats can be rendered resistant to EAE by immunization with synthetic peptides representing sequences contained within the V beta, J alpha and VDJ beta regions of the TCR that are conserved among encephalitogenic T cells. We propose that the mechanism of immunoregulation thus produced results from the stimulation of an anticlonotypic response directed at endogenously synthesized TCR peptides presented by Class I MHC on the surface of the autoreactive T cell, and that this mechanism may be part of the natural immunoregulation of T cell responses. The experimental data demonstrate the utility of this therapeutic approach and its potential for treatment of any pathogenic condition mediated by specific, oligoclonal T cell populations.

Spurious DNA blot hybridization resulting from bacterial contamination of primary tissue preparations

We have observed, by Southern blot hybridization, numerous episomes in DNA prepared from tumors grown as athymic mouse xenografts. These extrachromosomal DNAs were present in multiple copies and existed as relaxed and supercoiled conformational isomers. The episomes were readily detected with pBR322 plasmid probes, but not with purified plasmid inserts. Subsequently, four species of bacteria were isolated from tumor xenografts, suggesting that the pBR322 related episomes which we observed were bacterial DNAs, copurified during the isolation of xenograft DNA. This finding illustrates a potential problem which may be encountered in blot hybridizations utilizing nucleic acids from primary tissue preparations.