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Cutting edge: MHC class I triggering by a novel cell surface ligand costimulates proliferation of activated human T
S Agrawal1, J Marquet, G J Freeman
1Institut National de la Santé et de la Recherche Médicale U448, Henri Mondor Hospital, Faculté de Medecine, Créteil, France.
Insights
BY55 is a novel natural killer (NK) receptor that binds to MHC class I molecules. This interaction provides a costimulatory signal for T cell proliferation, particularly in activated T cells.
Area of Science:
- Immunology
- Cell Biology
Background:
- BY55 is a human cell surface molecule expressed on NK cells, CD8+ T lymphocytes, and intestinal intraepithelial T lymphocytes.
- The function of BY55 in immune cell interactions is not fully understood.
Purpose of the Study:
- To characterize BY55 as a novel NK receptor.
- To investigate the functional consequences of BY55-MHC class I interactions on T cells.
Main Methods:
- Utilized BY55 transfectants to study interactions with MHC class I molecules.
- Assessed T cell proliferation in response to BY55 triggering and MHC class I ligation.
Main Results:
- BY55 exhibits broad specificity for classical and nonclassical MHC class I molecules, requiring aggregation for optimal binding.
- BY55 ligation on activated T cell clones delivers a potent proliferative signal when combined with CD3 mAb.
- This costimulatory effect is observed in activated, but not resting, peripheral blood T cells.
Conclusions:
- BY55 functions as a novel NK receptor with significant implications for T cell activation.
- MHC class I ligation via BY55 offers an alternative or additional costimulatory pathway to CD28, especially relevant for CD28- T cells like intestinal intraepithelial lymphocytes.
Abstract:
BY55 is a human cell surface molecule whose expression is restricted to NK cells, a subset of circulating CD8+ T lymphocytes, and all intestinal intraepithelial T lymphocytes. Here, we report that BY55 is a novel NK receptor showing broad specificity for both classical and nonclassical MHC class I molecules, and that optimal binding requires a prior aggregation of MHC class I complexes. Using BY55 transfectants, we have identified functional consequences of MHC class I/ligand interactions for the class I-bearing cell. The triggering of MHC class I molecules on human T cell clones by BY55 delivered a potent proliferative signal in the presence of soluble CD3 mAb. The costimulatory signal provided by MHC class I ligation was only seen in activated, and not resting, peripheral blood T cells. This observation represents an additional and/or alternative pathway to CD28 costimulation and may be of particular relevance in memory T cells lacking CD28, such as intestinal intraepithelial T lymphocytes, which are CD28- but BY55+.