Identification of Mycobacterial Ribosomal Proteins as Targets for CD4 T Cells That Enhance Protective Immunity in Tuberculosis.

remains a threat to global health, and a more efficacious vaccine is needed to prevent disease caused by We previously reported that the mycobacterial ribosome is a major target of CD4 T cells in mice immunized with a genetically modified strain (IKEPLUS) but not in mice immunized with BCG. Two specific ribosomal proteins, RplJ and RpsA, were identified as cross-reactive targets of , but the breadth of the CD4 T cell response to ribosomes was not determined. In the present study, a library of ribosomal proteins and -predicted peptide libraries were used to screen CD4 T cell responses in IKEPLUS-immunized mice. This identified 24 out of 57 ribosomal proteins distributed over both large and small ribosome subunits as specific CD4 T cell targets. Although BCG did not induce detectable responses against ribosomal proteins or peptide epitopes, the ribosomal protein RplJ produced a robust and multifunctional Th1-like CD4 T cell population when administered as a booster vaccine to previously BCG-primed mice. Boosting of BCG-primed immunity with the RplJ protein led to significantly reduced lung pathology compared to that in BCG-immunized animals and reductions in the bacterial burdens in the mediastinal lymph node compared to those in naive and standard BCG-vaccinated mice. These results identify the mycobacterial ribosome as a potential source of cryptic or subdominant antigenic targets of protective CD4 T cell responses and suggest that supplementing BCG with ribosomal antigens may enhance protective vaccination against .