INDUCTION OF CYTOTOXIC T LYMPHOCYTE RESPONSE BY HLA CLASS IA RESTRICTED EPITOPES OF MYCOBACTERIAL HEAT SHOCK PROTEIN 65

摘要

The induction of HLA-A*0201 restricted CD8+ T cell responses against an immunodominant and highly conserved antigen of mycobacteria (hsp65) in HLA-A*0201/Kb (A2/Kb) transgenic mice and humans is disclosed. At least six high affinity HLA-A*0201 binding CTL epitopes are described, one of which appears to be identical in a large number of pathogenic bacteria, and is recognized in a CD8 independent fashion. This peptide induces CD8+ T cells both in humans and in HLA-A*0201/Kb transgenic mice, which respond to the mycobacterial hsp65 epitope pulsed target or BCG infected macrophages but not to un-infected macrophages or to the same target pulsed with the corresponding human hsp65 homologue. The mycobacterial hsp65 epitope is generated efficiently, whereas the human hsp65 homologue fails to be processed, thus avoiding induction of autoreactivity. Thus, herein described are high affinity HLA class I binding epitopes that are naturally processed and are recognized efficiently by HLA class I restricted CD8 T cells thereby affording sub-unit vaccines against tuberculosis and other infectious diseases.