The expression of both MHC class I and MHC class II molecules is regulated by cytokines, in particular, interferons, released in the course of an immune response. Interferon-α (IFN-α) and IFN-β increase the expression of MHC class I molecules on all types of cells, whereas IFN-γ increases the expression of both MHC class I and MHC class II molecules, and can induce the expression of MHC class II molecules on certain cell types that do not normally express them. Interferons also enhance the antigen-presenting function of MHC class I molecules by inducing the expression of key components of the intracellular machinery that enables peptides to be loaded onto the MHC molecules.
4-20 A distinct subset of T cells bears an alternative receptor made up of γ and δ chains.
During the search for the gene for the TCRα chain, another T-cell receptor-like gene was unexpectedly discovered. This gene was named TCRγ, and its discovery led to a search for further T-cell receptor genes. Another receptor chain was identified by using antibody against the predicted sequence of the γ chain and was called the δ chain. It was soon discovered that a minority population of T cells bore a distinct type of T-cell receptor made up of γ:δ heterodimers rather than α:β heterodimers. The development of these cells is described in Sections 8-11 and 8-12.
Like α:β T cells, γ:δ T cells can be found in the lymphoid tissues of all vertebrates, but they are also prominent as populations of intraepithelial lymphocytes, particularly in the skin and female reproductive tracts, where their receptors display very limited diversity. Unlike α:β T cells, γ:δ T cells do not generally recognize antigen as peptides presented by MHC molecules, and γ:δ T-cell receptors are not restricted by the ‘classical’ MHC class I and class II molecules that function in binding and presenting peptides to T cells. Instead, γ:δ T-cell receptors seem to recognize their target antigens directly and thus probably are able to recognize and respond rapidly to molecules expressed by many different cell types. Their ligands have been difficult to identify, but several have now been described and seem to indicate that γ:δ T cells play an intermediate, or transitional, role between wholly innate and fully adaptive immune responses.
Like NK-cell receptor ligands, such as the proteins MIC and RAET1 (see Section 3-27), many of the ligands seen by γ:δ T cells are induced by cellular stress or damage. γ:δ T cells may also bind antigens presented by ‘nonclassical’ MHC class Ib molecules, which we will discuss in Chapter 6. These proteins are related structurally to the MHC proteins we have already discussed, but have functions besides binding peptides for presentation to T cells. Additional ligands may include heat-shock proteins and nonpeptide ligands such as phosphorylated ligands or mycobacterial lipid antigens. γ:δ T cells can also respond to unorthodox nucleotides and phospholipids. Recognition of molecules expressed as a consequence of infection, rather than recognition of pathogen-specific antigens themselves, distinguishes intraepithelial γ:δT cells from other lymphocytes, and this would place them in the innate-like class. For these reasons, the term ‘transitional immunity’ has been proposed to clarify the role of γ:δ T cells, since the function of these cells seems to be someplace between innate and adaptive responses.