Major Histocompatibility Complex class II mRNAs encode heterodimeric proteins involved in the presentation of exogenous antigens during immune response. Their 3'UTRs bind a protein complex in which we identified two factors: EBP1, an Erb3 receptor-binding protein, and DRBP76, a double-stranded RNA-binding Nuclear Protein, also known as Nuclear Factor 90. Both are well characterized regulatory factors of several mRNA molecules processing. Using either EBP1 or DRBP76/NF90 specific knockdown experiments, we established that the two proteins play a role in regulating the expression of HLA-DRA, HLA-DRB1 and HLA-DQA1 mRNAs levels. Our study represents the first indication of the existence of a functional unit that includes different transcripts involved in the adaptive immune response. We propose that the concept of “RNA operon” may be suitable for our system in which MHCII mRNAs are modulated via interaction of their 3’UTR with same proteins.