At a more detailed level it is likely that the exact peptides targeted, their ability to mutate and escape T cell recognition and the sensitivity of the individual

T cells to peptide all play a major role. All these factors have been under intense scrutiny in HIV and, to a lesser extent, in HCV infection. T cells that are able to recognize the same peptide bound to major histocompatibility complex (pMHC) vary in their sensitivity for antigen by several orders of magnitude [6,7] and it has been shown in both murine models and human infection that CD8+ CTLs that are able to recognize very low antigen densities are most MK-8669 efficient at eliminating viruses [6,8–10]. A number of factors contribute to the sensitivity of the CTL response. On the T cell side this is determined in large part by T cell receptor (TCR) affinity, but also the level of TCR expression, TCR valency CD8 expression and expression of accessory molecules on the CTL clones comprising a polyclonal response. On the antigen-presenting cell or infected target cell, a major contributor to the ability of T cells to recognize low levels of antigen is the processing

and binding of peptide to MHC class I (MHCI). T cell sensitivity has been referred to in the literature as ‘functional avidity’. However, there are recent data to suggest that sensitivity is not an entirely fixed property and sensitivity SAHA HDAC ic50 can be fine-tuned in response to other factors such as cytokines and antigen level [11]. We therefore propose the use of the term ‘functional sensitivity’ in place

of ‘functional avidity’, as it is usually the sensitivity (which is determined by all of the above) rather than the actual avidity of the interaction that has been measured. In principle, increased functional sensitivity by definition allows T cells to recognize lower levels of peptide and thus target cells early in infection, or overcome immune evasion mechanisms such as down-regulation of MHCI. Because responses to different peptides, different HLA alleles or in different individuals might comprise Protirelin cells bearing different T cell receptors, it is plausible that such variation may contribute to the efficacy of T cell responses. Induction of functional, long-lived CD8+ T cell responses requires interaction with a professional antigen-presenting cell, its co-stimulatory molecules and help from CD4+ T cells. Once primed, CTL effector function is activated upon engagement between the T cell receptor (TCR) and cognate pMHCI [12], expressed on the surface of almost all nucleated cells. On interaction of a TCR with its cognate pMHCI there is ultimately a formal assembly of these molecules with the formation of an immunological synapse.