Brief Introduction to T10/T22
Major histocompatibility complex (MHC) class I molecules are a family of structurally related proteins that are widely expressed to present epitopes or antigens to killer T lymphocytes triggering an immediate response. There are two major subgroups of MHC class I molecules, one is classical MHC class I (also named as MHC class Ia) presenting antigens to the CD8+ T lymphocytes, and the other is non-classical molecules (MHC class Ib) with a limited polymorphism that is recognized by specific subsets of T cell receptors and other innate immune receptors.
T10 and T22 are two murine highly related MHC class Ib proteins that have been identified as specific ligands for γδ T cells. The murine T22 protein shares some similarities to the other MHC class Ia molecules in the crystal structure. The α chain of MHC class Ia usually folds into 3 domains, α1, α2, and α3 domains, of which α1 and α2 domains are essential for peptide binding and αβ T-cell recognition. In T22 protein, the α2 helix is incomplete, and the β sheet platform domain is exposed, which maybe the binding site for the γδ T-cell receptor.
Fig.1 Crystal structure of T22 compared with HLA-A2 and MICA. (Steele, 2000)
T10 and T22 Are Specific Ligands for γδ T Cell
The human γδ T cell is a subcategory of T lymphocytes carrying an alternative γδ T-cell receptor (γδ-TCR). Although only accounting for <5% of the total T cells, γδ T cells play an important function in both innate and adaptive immune responses by reacting with a spectrum of ligands and antigens.
Although the majority of MHC class Ib proteins are ligands recognized by αβ TCRs of T lymphocytes, the T22/T10 proteins are specific two ligands for γδ T cells. It has been reported that G8 γδ T cell clones developed and reacted with T22/T10 proteins in β2-microglobulin knockout mice. Another γδ TCR clone, KN6 γδ T cell line, might bind to and interact with T22 at an angle through the conserved motif in the CDR3δ loop. The binding of γδ-TCR to T22 is greatly different from the reaction of αβ TCRs with MHC molecules, by which interact with the MHC molecules using the CDR1 and CDR2 of α chain and β chain and interact with peptide using CDR3. However, the effector functions and biological significance of γδ T cell recognition and activation by T10/T22 ligands remain to be explored and elaborated, despite it has been proposed to be related to cell stress.
Fig.2 Upregulation of inducible MHC class Ib molecules, such as T22/T10 or MICA, leads to γδ T-cell activation. (Steele, 2000)
- Steele, C.R., et al. γδ T cell: Non-classical ligands for non-classical cells. Current Biology. 2000, 10(7): R282-R285.
- Wingren, C., et al. Crystal structure of a gammadelta T cell receptor ligand T22: a truncated MHC-like fold. Science. 2000, 287(5451): 310-314.