BY55/CD160 acts as a co-receptor in TCR signal transduction of a human circulating cytotoxic effector T lymphocyte subset lacking CD28 expression.
In the present study, we examined the role of the recently identified glycosylphosphatidylinositol (GPI)-anchored cell surface molecule BY55, assigned as CD160, in TCR signaling. CD160 is expressed by most intestinal intraepithelial lymphocytes and by a minor subset of circulating lymphocytes including NK, TCRgammadelta and cytotoxic effector CD8bright+CD28- T lymphocytes. We report that CD160, which has a broad specificity for MHC class Ia and Ib molecules, behaves as a co-receptor upon T cell activation. Anti-CD160 mAb enhance the CD3-induced proliferation of freshly isolated CD160-enriched peripheral blood lymphocytes and CD160+ T cell clones. Further, the engagement of CD160 receptors on normal clonal T lymphocyte populations lacking CD4, CD8 and CD28 molecules by MHC class I molecules results in an increased CD3-induced cell proliferation. Further, we found that CD160 co-precipitates with the protein tyrosine kinase p56lck and tyrosine phosphorylated zeta chains upon TCR-CD3 cell activation. Thus, we demonstrate that CD160 provides co-stimulatory signals leading to the expansion of a minor subset of circulating lymphocytes including double-negative CD4/CD8 T lymphocytes and CD8bright+ cytotoxic effector T lymphocytes lacking CD28 expression.
Nikolova
Maria
M
INSERM 448, Faculté de Médecine de Créteil, 8 rue du général Sarrail, 94010, France.
Marie-Cardine
Anne
A
Boumsell
Laurence
L
Bensussan
Armand
A
D000911:Antibodies, Monoclonal / Q000378:metabolism; D015703:Antigens, CD; D018106:CD28 Antigens / Q000378:metabolism*; D017252:CD3 Complex / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D058851:GPI-Linked Proteins; D005805:Genes, MHC Class I; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology; D011971:Receptors, Immunologic; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000145:classification / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000145:classification / Q000276:immunology*; D014162:Transfection
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C114505:CD160 protein, human; D018106:CD28 Antigens; D017252:CD3 Complex; D058851:GPI-Linked Proteins; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011971:Receptors, Immunologic