Identification and characterization of a naïve CD 8+ T cell repertoire for benzylpenicillin
Résumé
Summary Background Beta‐lactams allergy is the most commonly reported drug allergy and constitutes an important health problem. We previously showed the pre‐existence of a naïve CD 4+ T cell repertoire for benzylpenicillin ( BP ) coupled to human serum albumin ( HSA ) but little is known about the naïve CD 8+ T cell repertoire specific for BP . Objective The purpose of this work was to identify naïve CD 8+ T cells specific for BP and to explore mechanisms dictating their activation. Methods Co‐cultures were established with naïve CD 8+ T cells and autologous dendritic cells ( DC s) loaded with HSA ‐ BP or free BP . T cells were restimulated once a week with autologous DC s loaded with HSA ‐ BP or BP . The specific CD 8+ T cell response was measured using an IFN ‐γ ELIS pot assay. Results When using free BP , we were able to detect a naïve CD 8+ T cell repertoire for BP in the 6 out of 7 tested healthy donors. However, our results showed that HSA ‐ BP was recognized by naïve CD 8+ T cells in only one donor out of five tested healthy donors. Using free BP , we evidenced its binding to cellular proteins in DC s that was concentration dependent and was correlated with BP ‐specific CD 8+ T cell activation. Moreover, the BP ‐specific CD 8+ cell response was MHC class I‐dependent and required intracellular processing and proteasome activity. Conclusion and clinical relevance This work showed the existence of a naïve CD 8+ T cell repertoire for BP when DC s were treated with free BP suggesting that patients could be immunized by haptenated peptides from cellular proteins generated in antigen‐presenting cells.