The innate and adaptive immune systems intertwine in mounting an effective immune response against invading pathogens. The activation of innate immune components is often a prerequisite for the initiation of the adaptive immune response. The Pellino family consists of a 3-membered family of E3 ubiquitin ligases (Pellino 1, Pellino 2, and Pellino 3) that play important roles in immunity by catalysing post-translational modification of important signalling molecules. Pellino proteins have been widely studied for their roles in innate immunity. Nevertheless, emerging reports have highlighted the potential of Pellino proteins in regulating adaptive immune system. This thesis aims to further the knowledge in this area by performing the first systematic characterisation of the role of Pellino proteins in generating adaptive immune cell populations. To this end novel genetic models were generated resulting in mice that lack individual and combination of the Pellino family. Such models allowed for the first time to investigate potential functional interactions between the Pellino family members. While Pellino 3 does not mediate the production of various T and B cell subsets, Pellino 2 has a role in CD4 and CD8 T cell activation that is dependent on age. Importantly, the findings also highlight a selective role for Pellino 1 in negatively regulating the generation of activated CD4 and CD8 T cells, as well as germinal centre B cells and plasma cells in both young (10-12 weeks old) and aged (6 months old) mice. Interestingly, Pellino 1 and Pellino 2 exhibit distinctive functional roles in mediating CD8 T cell activation as individual deficiency of Pellino 1 and Pellino 2 favours its differentiation into CD8+ effector memory (Tem) and central memory (Tcm) cells, respectively. This suggests that they might have different physiological roles in controlling cytotoxic functions of Tem cells or systemic infections through Tcm cells. It was also found that Pellino 1 negatively modulates IL-17 production in Th17 cells. The mechanistic basis to the role of Pellino 1 in controlling T cell activation and IL-17 production is also explored. The studies conclude that this regulatory function of Pellino 1 is intrinsic to T cells and not antigen presenting cells. Overall, this body of work provides novel insight into the role of Pellino proteins, particularly Pellino 1, in the adaptive immune system. It also forms a foundation for future research to elucidate the physiological role of Pellino 1 in Th17 cell differentiation and may represent a new pathway that may be open to therapeutic exploitation in the treatment of inflammatory diseases.