Pilot Award Recipient: Magali Moretto, PhD

Early CD8 T cell Response to Microsporidia

March 01, 2012

In recent years, microsporidia species have rapidly emerged as human enteric pathogens in HIV infected individuals. Using E. cuniculi as a model of microsporidial infection, our laboratory has demonstrated the critical role of T cell for protection against these pathogens. Since E. cuniculi is a zoonotic infection, in depth study of gut mucosal immune response against this pathogen is essential. Reports from our laboratory have demonstrated that per-oral infection with E. cuniculi generates an early and strong intraepithelial lymphocytes (IEL) response and CD8+ population plays a central role in protection against the pathogen. Lately, the use of tetramer technology has allowed in depth study of systemic CD8+ T cell immune response to a number of viral and bacterial infections. As antigen(s) involved in the elicitation of CD8+ T cell immunity have not been identified, reagents needed to determine the magnitude and quantum of this response against the infection cannot be generated. Recent study and preliminary data presented in this proposal strongly suggest that polar tube protein 1 (PTP1) from E. cuniculi contains at least one immunodominant CD8+ specific epitope. Thus, this protein is an obvious candidate for further screening to identify CD8+ T cell epitopes which can ultimately lead to the generation of much needed tetramers. Furthermore, these tools will allow us to focus on CD8+ IEL in response against this important gut pathogen, which according to recent studies poses a major problem for HIV infected subjects.