High-avidity CD8+ T cells: optimal soldiers in the war against viruses and tumors.
ABSTRACT The primary goal of vaccination is the establishment of protective immunity. Thus there has been significant effort put toward the identification of attributes of the immune response that are associated with optimal protection. Although the number of virus-specific cells elicited is unquestionably important, recent studies have identified an additional parameter, functional avidity, as critical in determining the efficiency of viral clearance. T-cell avidity is a measure of the sensitivity of a cell to peptide antigen. High-avidity cells are those that can recognize antigen-presenting cells (APC) bearing very low levels of peptide antigen, whereas low-avidity cells require much higher numbers of peptide major histocompatibility complex (MHC) complexes in order to become activated or exert effector function. We are only now beginning to gain insights into the molecular control of avidity and the signals required for the optimal activation, expansion, and retention of high-avidity cells in vivo. This review summarizes the current knowledge regarding CD8+ T-cell avidity and explores some of the important issues that are, as of yet, unresolved.
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ABSTRACT: Virus-specific T cell responses are often directed to a small subset of possible epitopes and their relative magnitude defines their hierarchy. We determined the size and functional avidity of 4 representative peptide-specific CD8(+) T cell populations in C57BL/6 mice at different time points after lymphocytic choriomeningitis virus (LCMV) infection. We found that the frequency of different peptide-specific T cell populations in the spleen changed independently over the first 8 days after infection. These changes were not associated with a larger or more rapid increase in functional avidity and yet still resulted in a shift in the final immunodominance hierarchy. Thus, the immunodominance observed at the peak of an antiviral T cell response is not necessarily determined by the initial size or rate of functional avidity maturation of peptide-specific T cell populations.Virology 07/2009; 390(2):197-204. DOI:10.1016/j.virol.2009.05.021 · 3.28 Impact Factor
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ABSTRACT: Cell-based cancer vaccines are a highly attractive alternative to standard cancer therapies. They theoretically have the capability of inciting a multitargeted therapeutic response that functions by reshaping the host-tumor interaction, tipping the balance in favor of tumor rejection. Due to the polyclonal immune response induced, they are less likely to result in therapeutic escape than most cancer treatments in use today. Their immune-based mechanism of action offers a unique approach to management that should not be limited by traditional modes of drug resistance. Their favorable side-effect profile further identifies them as a potential treatment modality of choice. Despite these positive features, a number of hurdles must be overcome in order for cancer vaccines to take their place in the clinic as part of standard cancer therapy. Vaccine protocols must be optimized both to induce a high-quality antitumor T-cell response and to abrogate established mechanisms of immune tolerance that actively function to shut antitumor T cells down. By applying basic knowledge of the molecular features of T-cell biology and immune tolerance to the design of trials that combine tumor vaccines with targeted immunomodulatory drugs, potent strategies for inducing effective antitumor immunity can be developed. The first of these combinatorial trials have already been reported and offer a tantalizing glimpse of the future of cancer immunotherapy.International Reviews Of Immunology 08/2009; 25(5-6):415-43. DOI:10.1080/08830180600992423 · 5.28 Impact Factor