Cancer immunotherapy relies on the ability of the immune system to target tumor-specific antigens to generate an immune response. This initial response requires both binding of the MHC/antigen peptide to T-cell receptor complex, along with a second costimulatory signal created by the binding of CD28 on the T cell, with B7 located on the antigen-presenting cell. Regulatory checkpoints, such as c...

Cytotoxic T lymphocytes (CTL) protect against viruses including HIV-1. To avoid viral escape mutants that thwart immunity, we chose 25 CTL epitopes defined in the context of natural infection with functional and/or structural constraints that maintain sequence conservation. By combining HLA binding predictions with knowledge concerning HLA allele frequencies, a metric estimating population prot...

Cytotoxic T lymphocytes (CTL) lyse antigen-bearing target cells by two distinct pathways. Whereas granule exocytosis targets any antigen-bearing cell, fas-mediated cytotoxicity kills only fas-expressing cells and does not require antigen expression. Fas pathway activation can potentially lead to lysis of uninfected bystander cells. We examined the relative usage of the two pathways by CTL clone...

The differentiation of cytotoxic T lymphocyte precursor cells (CTL-P) into CTL effector cells is a two-step process. In the first step, naïve CTL-P (CTL-PN) become activated (CTL-PA) but do not yet have the capacity to kill target cells. CTL-PA can be distinguished from CTL-PN because the former are far less sensitive than the latter to the effects of in vitro-generated suppressor cells. Thus, ...