Role of T Cells in Immune Responses
2-1 T cell receptor (TCR) complex. The TCR consists of α and β subunits (most common) or γ and δ subunits, which recognize antigen in association with major histocompatibility complex molecules. Differences in the variable (V) regions of the TCR subunits account for the diversity of antigenic specificity among T cells. Activation of T cells requires the closely associated CD3, a complex of four different types of subunits. C, constant region; V, variable region.
2-2 Overview of T cell activation. The dendritic cell (DC) initiates an interaction with CD4 or CD8 T cell through an MHC-peptide interaction with the T cell receptor. The DC provides an 11–amino acid peptide on the class II MHC, B7 coreceptor, and cytokines to activate CD4 T cells. Activation of CD8 T cell is through the class I MHC and 8– to 9–amino acid peptide plus the B7 coreceptor and cytokines. Presentation of antigen to CD4 T cells and cross presentation to CD8 T cells is shown in the diagram. The cytokines produced by the DC determine the type of T helper cell. Activated CD8 T cells can interact with and lyse target cells through T cell receptor recognition of peptide in class I MHC molecules on target cell. APC, antigen-presenting cell; CTL, cytotoxic T lymphocyte; Ig, immunoglobulin.
2. Effective stimulation requires primary and coactivating signals (fail-safe mechanism) that trigger intracellular signal transduction cascades, ultimately resulting in new gene expression (Fig. 2-3).
2-3 Cell-cell interactions that initiate and deliver T cell responses. A, Dendritic cells initiate specific immune responses by presenting antigenic peptides on class II MHC molecules to CD4 T cells with binding of coreceptors and release of cytokines. B, CD4 T cells activate B cells, macrophages, and dendritic cells (antigen-presenting cells [APCs]) by adding the CD40 ligand (CD40L) binding to CD40 and cytokines. C, CD8 cytotoxic lymphocytes (CTLs) recognize targets through T cell receptor and CD8 binding to antigenic peptides on class I major histocompatibility (MHC) molecules.
2-4 Structures of class I and II major histocompatibility complex (MHC) molecules. Class I molecules comprise a large α chain and a much smaller β2-microglobulin molecule (β2m), which is encoded by a gene located outside of the MHC. The class I peptide binding site is a pocket-like cleft (like pita bread) that holds peptides of 8 to 10 residues. Class II molecules comprise α and β chains of about equal size. The class II peptide binding site is an open-ended cleft (like a hotdog roll) that holds peptides with 12 or more residues. Noncovalent interactions hold the subunits together in both class I and II molecules.