Dr. Peterlin studies the regulation of expression of genes that have immunological significance. A major effort of his laboratory is directed towards the elucidation of a normal and aberrant expression of major histocompatibility complex (MHC) class II proteins that lead to immunodeficiency and autoimmunity. Thus, he is following pathways of antigen processing and presentation and T cell responses at the molecular level. In addition, his studies have elucidated mechanisms of action of accessory and regulatory proteins encoded by the human immunodeficiency virus (HIV), which causes the acquired immunodeficiency syndrome (AIDS).
Major histocompatibility complex antigens or transplantation antigens are essential polymorphic determinants that specify antigen presentation and T cell help. They initiate and propagate normal and abnormal immune responses. They are peptide carriers that present antigens to the T cell antigen receptor and that allow for T cells to recognize specific B cell subpopulations. Absent expression of MHCII determinants results in poor T cell development, lack of mature peripheral T cell populations, and severe combined immunodeficiency (bare lymphocyte syndrome). Surprisingly, differential expression of MHCII determinants can also result in autoimmunity or agammaglobulinemia. Dr. Peterlin studies the genetic bases of the BLS and its affected genes. These regulatory proteins and their genes are used to reproduce BLS and create new models of autoimmune diseases in mice. For example, targeting the expression of MHCII determinants and costimulatory molecules to chondrocytes and synoviocytes has also created a new model of inflammatory arthritis in the mouse. Doing the same to tumor cells (breast carcinoma) resulted in effective immunotherapy against the disease.
Other projects relate to accessory and regulatory proteins of HIV. Dr. Peterlin has studied cellular factors that activate latent proviruses in infected cells. These include NF-kB and NF-AT, which are two nuclear transcription factors. In addition, his laboratory contributed to our understanding of mechanisms of action of viral proteins Nef and Tat. Tat is a trans-activator and an RNA-binding protein. Interactions between Tat and TAR, its RNA target, result in greatly increased rates of elongation of transcription. Thus, the study of cyclin dependent kinases that interact with Tat started a new direction in eukaryotic transcription. The complex regulation of these cyclin dependent kinases also dictates cellular differentation and proliferation as well as proviral latency in the host. Nef was demonstrated not only to activate cells but to facilitate the formation of optimal virions for subsequent rounds of infection. Additionally, he studies Vif and APOBEC family members, which edit RNA and contribute to genomic stability of the organism. Major efforts of the laboratory try to abrogate the viral reservoir in the host, i.e. to render HIV-1 an acute infection. Others focus on structural/functional studies of these other intriguing retroviral complexes in cells.