17.1 Activation of T lymphocyte

The activation of T lymphocyte is done by antigen loaded over the MHC molecules. Proliferation of T lymphocytes and there differentiation into effector and memory cells requires different co-stimulatory molecules in addition to antigen presenting cells. A T lymphocyte recognizes only the protein antigens that are loaded over the MHC molecule. Sometimes chemicals entering the body through skin also induce the T cell immune responses and are often called contact sensitivity reactions. Differentiated effector T-cells following antigen sensitization produce an effective immune response.

17.2 Co-stimulatory molecules

A naïve T lymphocyte proliferates and differentiates into effector cell with the help of signals provided by antigen presenting cells, and are called as co-stimulatory molecules. In absence of co-stimulation, antigen sensitized T cells either die by apoptosis or do not produce an effective immune response. The best known co-stimulatory molecules are B7-1(CD80) and B7-2(CD86) that are expressed on activated antigen presenting cells. Their ligands are present over the surface of T-cell and are called as CD28. The antigen presenting cells which do not produce any co-stimulatory molecules fail to produce any T-cell immune response. The activated T lymphocyte also expresses CD40 ligands which binds with CD40 present over the antigen presenting cells. The activation of T-cells follows a cascade.

Naïve T-cells activated by peptide MHC complex causes the expression of CD 40 ligand (CD40L) on T-cell. CD40L binds to CD40 present on dendritic cells or antigen presenting cells which lead to expression of B7-1 and B7-2 molecules that binds to CD28 receptor present over the T-lymphocyte. In addition activated dendritic cell also secretes cytokines such as IL-12 which further stimulates the proliferation and differentiation of T-lymphocytes.

The activation of T-lymphocyte by CD28 involves activation of MAP (Mitogen activated protein) kinase pathway (MAP). MAP kinase stimulates the expression of antiapoptotic Bcl-xL, and Bcl-2 which leads to prolonged cell survival. In addition secretion of IL-2 and other cytokines promotes proliferation and differentiation of T-lymphocytes. The homeostasis of T-cell activation is modulated by inhibitors of CD28.The inhibitors of CD28 are cytotoxic T-lymphocyte antigen4 (CTLA-4) and Programmed death -1 (PD-1). CTLA-4 has a very high affinity for co-stimulatory molecule B7-1 and B7-2 . Once activated CTLA-4 completely inhibits the access of CD28 to B7 co-stimulatory molecules.