synthetic mycobacterial molecular patterns partially complete freunds adjuvant complete freunds adjuvant cfa has historically been one of the most useful tools of immunologists essentially comprised of dead mycobacteria and mineral oil we asked ourselves what is special about the mycobacterial part of this adjuvant and could it be recapitulated synthetically here we demonstrate the essentiality of nglycolylated peptidoglycan plus trehalose dimycolate both unique in mycobacteria for the complete adjuvant effect using knockouts and chemical complementation a combination of synthetic nglycolyl muramyl dipeptide and minimal trehalose dimycolate motif glcc14c18 was able to upregulate dendritic cell effectors plus induce experimental autoimmunity qualitatively similar but quantitatively milder compared to cfa this research outlines how to substitute cfa with a consistent molecularlydefined adjuvant which may inform the design of immunotherapeutic agents and vaccines benefitting from cellmediated immunity we also anticipate using synthetic microbeassociated molecular patterns mamps to study mycobacterial immunity and immunopathogenesis