The adaptive immune system relies on B and T lymphocytes to ensure a specific and long-lasting protection of an individual from a wide range of potential pathogenic hits. Lymphocytes are highly potent and efficient in eliminating pathogens. However, lymphocyte activation must be tightly regulated to prevent incorrect activity that could result in immunopathologies, such as autoimmune disorders or cancers. Comprehensive insight into the molecular events underlying lymphocyte activation is of enormous importance to better understand the function of the immune system. It provides the basis to design therapeutics to regulate lymphocyte activation in pathological scenarios. Most reported defects in immunopathologies affect the regulation of intracellular signaling pathways. This highlights the importance of these molecules, which control lymphocyte activation and homeostasis impacting lymphocyte tolerance to self, cytokine production and responses to infections. Most evidence for these defects comes from studies of disease models in genetically engineered mice. There is an increasing number of studies focusing on lymphocytes derived from patients which supports these findings. Many indirectly involved proteins are emerging as unexpected regulators of the immune system. In this mini-review, we focus in proteins that regulate plasma membrane (PM) compartmentalization and thereby impact the steady state and the activation of immunoreceptors, namely the T cell antigen receptor (TCR) and the B cell antigen receptor (BCR). Some of these membrane proteins are shown to be involved in immune abnormalities; others, however, are not thoroughly investigated in the context of immune pathogenesis. We aim to highlight them and stimulate future research avenues.

Hepatitis C virus (HCV) infection is probably the most common chronic viral infection and affects an estimated 180 million people worldwide, accounting for 3% of the global population. Although the liver is considered to be the primary target, extrahepatic manifestations are well recognized among patients with chronic HCV infection. Epidemiological studies have clearly demonstrated a correlation between chronic HCV infection and occurrence of B-cell non-Hodgkin's lymphomas (B-NHL). The clinical evidence that antiviral therapy has a significant role in the treatment at least of some HCV-associated lymphoproliferative disorders, especially indolent B-NHL, further supports the existence of an etiopathogenetic link. However, the mechanisms exploited by HCV to induce B-cell lymphoproliferation have so far not completely clarified. It is conceivable that different biological mechanisms, namely, chronic antigen stimulation, high-affinity interaction between HCV-E2 protein and its cellular receptors, direct HCV infection of B-cells, and "hit and run" transforming events, may be combined themselves and cooperate in a multifactorial model of HCV-associated lymphomagenesis.

Hepatitis C virus (HCV) encodes a single polyprotein, which is processed by cellular and viral proteases to generate 10 polypeptides. The HCV genome also contains an overlapping +1 reading frame that may lead to the synthesis of an additional protein. Until recently, studies of HCV have been hampered by the lack of a productive cell culture system. Since the identification of HCV genome approximately 17 years ago, structural, biochemical and biological information on HCV proteins has mainly been obtained with proteins produced by heterologous expression systems. In addition, some functional studies have also been confirmed with replicon systems or with retroviral particles pseudotyped with HCV envelope glycoproteins. The data that have accumulated on HCV proteins begin to provide a framework for understanding the molecular mechanisms involved in the major steps of HCV life cycle. Moreover, the knowledge accumulated on HCV proteins is also leading to the development of antiviral drugs among which some are showing promising results in early-phase clinical trials. This review summarizes the current knowledge on the functions and biochemical features of HCV proteins.