T cell activation leads to dramatic changes in cellular phenotype. We used activated human CD4 T cells to study how RNA binding proteins define the post-transcriptional landscape. Using RIPseq, we identified the RNA interactome of U2AF2 and show that U2AF2 binds the majority of transcripts that are differentially expressed and/or alternatively spliced during activation. Using RIP mass spectrometry, a unique protein interactome centered on U2AF2 is assembled by activation and comprised of both directly bound central members (RNAse-resistant) and indirectly bound peripheral members (RNAse-sensitive). Knocking down specific U2AF2 interactome members (U2AF1, SYNCRIP, SRRM2, ILF2) selectively affects cytokine secretion and activation markers. The expression and/or alternative splicing of transcripts important for immune cell function are also affected by knocking down these interactome members, both peripheral and central. Furthermore, we show that knockdown of interactome members can affect the proteins and transcripts bound to U2AF2, altering the transcriptome of activated T cells. Our work highlights the importance of understanding the assembly of RNA binding protein complexes as regulators of T cell activation and function.