T- cell help is always antigen specific. Only helper T cells that have responded to antigen previously presented in the con text of MHC class II can subsequently help those CD8+ T cells or CD19+ B cells that are already committed to the same antigen (Burnet’s clonal selection theory). Helper T cells recognize both antigen and MHC class II antigens as a complex on the presenting cells, via their specific TCR. They then recognize the same combination of antigen and the particular class II antigen on the responding cell. Co- stimulation is essential for T- cell activation and accessory molecules are vital (Fig. 1).
Fig1. (a, b) Role of co- stimulatory pathway in T- cell activation. APC, antigen- presenting cell; MHC, major histocompatibility complex.
MHC class II molecules play an important role in the activation of helper T cells. T cells from one individual will not cooperate with the APCs, T cells or B cells from a different person (i.e. of a different HLA type). Certain MHC class II molecules on the presenting cells fail to interact with particular antigens (as a prelude to triggering helper T cells) and so fail to trigger an adaptive immune response to that stimulus. This provides a mechanism for the genetic regulation of immune responses (originally attributed to distinct immune response genes). The MHC class II thus helps to determine the responsiveness of an individual to a particular foreign antigen, since they interact with the antigen before T- cell help can be triggered.
When helper T cells meet an antigen for the first time, there is a limited number that can react with that antigen to provide help; these stimulated T cells therefore undergo blast transformation and proliferation, providing an increased number of specific helper T cells when the animal is re- exposed, i.e. an expanded clone. In addition, specific memory T cells differentiate.
Memory T cells (which bear the surface marker CD45RO) have increased numbers of adhesion molecules (LFA- 1, CD2, LFA- 3, ICAM- 1) and a higher proportion of high- affinity receptors for the relevant antigen. Memory cells are therefore easily activated and produce high concentrations of IL- 2 to recruit more helper T cells of both types, Th1 and Th2 (see later in the chapter). Thus T- cell memory is a combi nation of an increase of T cells (quantitative) as well as a qualitative change in the efficiency of those T cells, providing a more rapid immune response on second and subsequent expo sure as well as a more vigorous response.
Antigen- specific cell- mediated effector responses are carried out by T lymphocytes. T cells can lyse cells expressing specific antigens (cytotoxicity), release cytokines that trigger inflammation (delayed- type hypersensitivity), take part in antibody production or regulate immune responses (regulation). Distinct T- cell populations mediate these types of T- cell responses: CD8+ Tc cytotoxic cells, CD4+ Th1 cells, CD4+ Th2 and CD4+ Treg cells, respectively.
