The 3′ CCACCA Sequence of tRNA Ala (UGC) Is the Motif That Is Important in Inducing Th1-Like Immune Response, and This Motif Can Be Recognized by Toll-Like Receptor 3

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Abstract
In this article, the immunogenicity of tRNA and the recognition of tRNA by Toll-like receptors (TLRs) are analyzed. Analyses of the effects of different tRNAAla(UGC) fragments (tRNAAla1-76 [corresponding to positions 1 through 76], tRNAAla26-76, tRNAAla40-76, tRNAAla62-76, tRNAAla1-70, tRNAAla26-70, tRNAAla40-70, and tRNAAla62-70) on the immune responses of hepatitis B surface antigen (HBsAg) were performed with BALB/c mice. Results show that tRNAAla1-76, tRNAAla26-76, tRNAAla40-76, and tRNAAla62-76 adjuvants not only induced stronger T helper (Th) 1 immune responses but also cytotoxic-T-lymphocyte (CTL) responses relative to tRNAAla1-70, tRNAAla26-70, tRNAAla40-70, and tRNAAla62-70 adjuvants in HBsAg immunization. A deletion of the D loop (tRNAAla26-76), anticodon loop (tRNAAla40-76), or TψC (tRNAAla62-76) loop of tRNAAla(UGC) does not significantly decrease the adjuvant characteristic of tRNAAla(UGC). However a deletion of the 3′-end CCACCA sequence (tRNAAla1-70, tRNAAla26-70, tRNAAla40-70, and tRNAAla62-70) of tRNAAla(UGC) significantly decreased the adjuvant characteristic in Th1 and CTL immune responses. Moreover, the recognitions of different tRNAAla(UGC) fragments by TLR3, TLR7, TLR8, and TLR9 were analyzed. Results show that a deletion of the 3′ CCACCA sequence of tRNAAla(UGC) significantly decreased the recognition by TLR3. We concluded that the 3′ CCACCA sequence of tRNAAla(UGC) is the important motif to induce Th1 and CTL responses and this motif can be effectively recognized by TLR3.