spp. are intracellular pathogenic bacteria remarkable in their ability to escape immune surveillance and therefore inflict a state of chronic disease within the host. To enable further immune response studies， was engineered to express the well-characterized chicken ovalbumin (OVA). Surprisingly， we found that CD8 T cells bearing T cell receptors (TCR) nominally specific for the OVA peptide SIINFEKL (OT-1) reacted to parental -infected targets as well as OVA-expressing variants in cytotoxicity assays. Furthermore， splenocytes from -immunized mice produced gamma interferon (IFN-γ) and exhibited cytotoxicity in response to SIINFEKL-pulsed target cells.To determine if the SIINFEKL-reactive OT-1 TCR could be cross-reacting to peptides， we searched the proteome using an algorithm to generate a list of near-neighbor nonamer peptides that would bind to H2K Selecting five peptide candidates， along with controls， we verified that several of these peptides mimicked SIINFEKL， resulting in T cell activation through the "SIINFEKL-specific" TCR. Activation was dependent on peptide concentration as well as sequence. Our results underscore the complexity and ubiquity of cross-reactivity in T cell recognition. This cross-reactivity may enable microbes such as to escape immune surveillance by presenting peptides similar to those of the host and may also lead to the activation of autoreactive T cells.