“Toll” protein was originally discovered as a developmental marker in fruit fly (Drosophila). Now Toll like receptor (TLR) is envisioned as one of the important innate immune group of receptors regulating mammalian immune system. Interestingly, TLR response has been translated in immuno-pathology of most of the diseases and its immune responses including tumor immunity, infection immunity and autoimmunity. Moreover, in very recent time, TLR response has been suggested to modulate cell mediated immunity (CMI). Accordingly, the new paradigm of TLR response in T cell proposes a challenging work of T cell biology, both in basic and in translational research. Here we have reviewed the structural and functional homology of “Toll” protein in Drosophila and mammalian TLR, role of TLR in innate immunity, adaptive immunity and immunotherapy, recent updates of TLR response in T cells and the yet unanswered questions on the role of TLR in T cells to explore the new paradigm of TLR as one of the important connecting bridges between innate and adaptive immunity.

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