Cutting edge: MHC class I triggering by a novel cell surface ligand costimulates proliferation of activated human T cells.
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+.
Agrawal
S
S
Institut National de la Santé et de la Recherche Médicale U448, Henri Mondor Hospital, Faculté de Medecine, Créteil, France.
Marquet
J
J
Freeman
G J
GJ
Tawab
A
A
Bouteiller
P L
PL
Roth
P
P
Bolton
W
W
Ogg
G
G
Boumsell
L
L
Bensussan
A
A
D000818:Animals; D015703:Antigens, CD; D018106:CD28 Antigens / Q000378:metabolism; D002460:Cell Line; D006224:Cricetinae; D058851:GPI-Linked Proteins; D015789:HLA-A2 Antigen / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D011971:Receptors, Immunologic / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D012995:Solubility; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014162:Transfection