T cells and antigen recognition

The immune response is broadly classified into either the innate, antigen-nonspecific response, or the adaptive, antigen-specific response. Leukocytes of the innate immune system reside in peripheral tissues and circulate through the blood and secondary lymphoid tissues (the spleen and the lymph nodes), serving as immunologic sentinels for detecting general signs of danger. Similarly, B and T lymphocytes traverse the body to mediate the adaptive immune response. These cells express a comprehensive repertoire of antigen-specific receptors (cell surface immunoglobulin receptors for B cells, and cell surface T cell receptors (TCR) for T cells) that can recognize over one million distinct antigens [1]. Whereas the B cell antigen receptor directly binds to antigenic determinants present on soluble proteins, carbohydrates, or nucleic acids, the T cell antigen receptor binds most commonly to short fragments of antigens that have been broken down and loaded onto Major Histocompatibility Complex (MHC) molecules. Thus, B cells can see antigen directly, and respond by differentiating into immunoglobulin-secreting plasma cells. In contrast, T cells see processed antigen in the context of self MHC molecules, thereby providing a basis for self-nonself discrimination [2]. Two major subsets of T cells collaborate to mediate an effective immune response. CD4⁺ helper T cells are activated after binding peptide antigen presented by MHC Class II molecules, and provide cytokine-mediated "help" both to shape the B cell-mediated humoral response, and to maximize the quality and durability of the CD8⁺ T cell-mediated cytotoxic T lymphocyte (CTL) response [3]. CD4⁺ T cells can be further divided into T helper type 1 cells, which secrete interleukin-2 (IL-2) and interferon-γto promote CTL activity, and T helper type 2 cells, which secrete interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-6 (IL-6), and promote humoral and allergic immune responses. Of these two T helper phenotypes, the T helper type 1 phenotype is generally considered to contribute more to antitumor immunity [4]. CTLs are activated after binding antigen presented by MHC Class I molecules, deploying a payload of cytokines and enzymes that can effectively lyse diseased cellular targets. Thus, it is CD8⁺ effector T cells that are critical for destroying host cells altered by either viral infection or oncogenic transformation.