Studies of human antiviral CD8+ lymphocytes using class I peptide tetramers

Abstract

Understanding the interactions between a host and a pathogen relies crucially on quantitative measurements of immune responses. Until recently, measurements of the levels of cellular immune responses, i.e. those mediated by CD4+ and CD8+ T lymphocytes have depended largely on culture in vitro and subsequent measurement of specific functions (such as cytolysis). More recently, new technologies based around tetrameric class I peptide complexes (tetramers) have allowed immunologists to measure CD8+ T lymphocyte levels directly ex vivo and independently of function. Since CD8+ lymphocytes play a key role in a number of important human viral infections, these tools have yielded useful insights into the dynamics, phenotype and function of human antiviral lymphocyte populations. In this review we describe some of the basic aspects of the biology of virus-specific CD8+ lymphocytes, and the current methods available to detect them. The use of tetramers has, in just four years, transformed our understanding of the immune responses against HIV, HTLV-1, HBV, HCV, CMV and EBV, and holds promise in a number of areas where quantitative analysis of the antiviral response in terms of both number and function is critical.

CCR5 in T Cell-Mediated Liver Diseases: What’s Going On?

“…Based on this, it was proposed that these cells could potentially curtail viral replication and hepatic injury during acute and chronic HCV infection by promoting Th1 responses via IFN-␥ production. In agreement with this hypothesis, an increased CD8 ϩ T cell response via IFN-␥ production was associated with viral clearance and recovery from acute HCV infection in patients (49) and in chimpanzees (50). Furthermore, a genetic predisposition to enhanced NK cell function (through IFN-␥ production) was reported to contribute to the spontaneous clearance of HCV in infected individuals (51).…”

Tumor-specific Ab-mediated targeting of MHC-peptide complexes induces regression of human tumor xenograftsin vivo

“…As shown in Fig. 1A, scHLA-A2-peptide complexes generated in the form of tetramers with melanoma differentiation antigen gp100 (16) or an Epstein-Barr virus (EBV)-derived peptide epitope (17) could stain specifically and with high avidity the corresponding T cells (Fig. 1 A).…”

“…1C). The inclusion bodies were isolated, solubilized, reduced, and refolded in vitro in the presence of HLA-A2-restricted peptides derived from the melanoma differentiation antigen gp100 T cell epitopes G9-209M and G9-280V (16) or the EBV-derived peptide GLC 280-288 (GLCTLVAML) derived from the EBV BMLF1 protein (17,20). ScHLA-A2͞scFv fusion molecules, containing the specific peptide used to stabilize the HLA-A2 complex, were purified from the refolding solution by ion-exchange chromatography by using Q-Sepharose columns.…”

“…As for the selection of the peptide epitope for the targeted MHC-peptide complex, it has been shown that CTL precursors directed against influenza, EBV, and cytomegalovirus epitopes (peptides) are maintained at high frequencies in the circulation of cancer patients and healthy individuals, and that these CTLs are usually active and possess a memory phenotype (17,20). Thus, these CTLs would be the source of choice to be redirected to the tumor cells through the use of a MHC-peptide͞scFv fusion molecule folded around such viral-derived epitopes, which was also demonstrated in this study.…”

Peripheral immunization induces functional intrahepatic Hepatitis C specific immunity following selective retention of vaccine-specific CD8 T cells by the liver

“…4 While it is known that a strong intrahepatic T-cell response is critical for clearance of HCV infection, up to 70% of infected individuals fail to either mount or sustain these responses resulting in chronic infection. 3 This failure may in part be due to the unique immunological properties of the liver and its ability to modulate T-cell responses.…”