T cells with a specific motif in the CDR3-beta region protect mice from CT26 tumor growth (131.46)

Abstract

Abstract Vaccination with peptide mimics of tumor antigens, or mimotopes, is a potential strategy for antigen-specific immunotherapy of cancer. To determine how to elicit the most effective antigen-specific cytotoxic response against tumors, we have assembled a set of mimotopes of AH1, the immunodominant antigen from the mouse CT26 tumor. Although the AH1 antigen is an ineffective immunogen, vaccination with some of the mimotopes is very successful in protecting mice from tumor growth. The majority of AH1-specific T cells responding to the vaccine or tumor express V-beta 8 gene segments. However, tumor protection by the mimotope vaccines correlates with stimulation of T cells with a more restricted TCR V-beta repertoire. These T cells express receptors that encode a relatively short CDR3-beta motif. This motif consists of a small amino acid, a non-hydrophobic amino acid, a germline-encoded tyrosine, and the J-beta 2.6 gene segment. These results suggest that protective mimotopes enhance antitumor immunity, in part, by increasing the expansion of a subset of functional tumor-specific T cells that naturally respond to the tumor, not a new repertoire of T cells only elicited by the mimotope. We will test the hypothesis that specific T cells with this motif impart increased protection because they have higher affinity for the antigen complex than specific T cells without the motif.