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Presentation of Nonprotein Antigens to T Cells

المؤلف:  Abbas, A. K., Lichtman, A. H., Pillai, S., & Henrickson, S. E.

المصدر:  Cellular and Molecular Immunology (2026)

الجزء والصفحة:  11E, P150-151

2026-06-04

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T cells also recognize and react against small molecules and even metal ions in an MHC-restricted manner. In fact, expo sure to some small molecules that are used as therapeutic drugs and to metals such as nickel and beryllium sometimes leads to pathologic T-cell reactions (so-called hypersensitivity reactions). There are several ways in which these nonpeptide antigens may be recognized by MHC-restricted CD4+ and CD8+ T cells. Some of the chemicals are thought to covalently modify self peptides or the MHC molecules themselves, creating altered molecules that are recognized as foreign. Other chemicals bind noncovalently to MHC molecules and alter the structure of the peptide-binding cleft such that the MHC molecule can display peptides that are not normally presented, and these peptide-MHC complexes are seen as being foreign.

Several small populations of T cells other than CD4+ and CD8+ cells are able to recognize nonprotein antigens without the involvement of MHC-I or MHC-II molecules. Thus, these populations are exceptions to the rule that T cells can see only MHC-associated peptides. The best defined of these populations are natural killer T (NKT) cells and γδ T cells.

NKT cells express markers that are characteristic of both NK cells and T lymphocytes and express αβ T-cell receptors with very limited diversity (see Chapter 10). NKT cells recognize lipids and glycolipids displayed by the MHC-I-like molecule called CD1. Several CD1 proteins are expressed in humans and mice. Although their intracellular traffic pathways differ in subtle ways, all CD1 molecules bind and display lipids by a unique mechanism. Newly synthesized CD1 molecules pick up cellular lipids and carry these to the cell surface. From here, the CD1-lipid complexes are internalized into endosomes or lysosomes, where lipids that have been ingested from the external environment are captured and new CD1-lipid complexes are then formed, which are returned to the cell surface. Thus, CD1 molecules acquire endocytosed lipid antigens during recycling and present these antigens without apparent processing. The NKT cells that recognize the lipid antigens may play a role in defense against microbes, especially mycobacteria (which are rich in lipid components).

γδ T cells are a small population of T cells that express antigen receptor proteins that are similar but not identical to the αβ receptors of CD4+ and CD8+ T cells. γδ T cells recognize many different types of antigens, including some proteins and lipids, as well as small phosphorylated molecules and alkyl amines. These antigens are not displayed by MHC molecules, and γδ cells are not MHC restricted. It is not known if a particular cell type or antigen display system is required for presenting antigens to these cells.