The nonclassical class I molecule CD1d associates with the novel CD8 ligand gp180 on intestinal epithelial cells.
Previous studies have shown that normal intestinal epithelial cells (IECs) are able to selectively activate CD8(+) T cells with suppressor activity, inducing proliferation associated with the activation of both the CD8-associated kinase p56(lck) and the T cell receptor (TCR)-associated kinase p59(fyn). This process appears to relate in part to a 180-kDa IEC surface glycoprotein, gp180, which binds to CD8 and activates CD8-associated p56(lck). However, purified gp180 alone is unable to induce T cell proliferation and does not activate p59(fyn). Because the class Ib molecule CD1d is expressed by IECs and monoclonal antibodies (mAbs) against CD1d inhibit IEC-induced proliferation of CD8(+) T cells, co-immunoprecipitation and enzyme-linked immunosorbent assay studies were performed, which demonstrated an association of gp180 and CD1d on the IEC surface. Interestingly, the activation of p59(fyn) in IEC-T cell co-cultures was blocked by the anti-CD1d mAb D5 but not by the anti-gp180 mAb B9. Conversely, treatment of IECs with mAb B9 inhibited IEC-induced activation of p56(lck) but not p59(fyn). More directly, a human CD1d cDNA (FO-1 D5) transfectant was able to activate p59(fyn) but not p56(lck). These data suggest that the CD1d-gp180 complex on the surface of IECs can be recognized by the TCR-CD8 co-receptor, resulting in the activation of CD8(+) T cells.
Campbell
N A
NA
Division of Clinical Immunology, Mount Sinai Medical Center, New York, New York 10029, USA. nicola@gene.com
Kim
H S
HS
Blumberg
R S
RS
Mayer
L
L
D000911:Antibodies, Monoclonal / Q000276:immunology; D018949:Antigens, CD1 / Q000276:immunology / Q000378:metabolism*; D055610:Antigens, CD1d; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D002460:Cell Line; D018920:Coculture Techniques; D004789:Enzyme Activation; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn
D000911:Antibodies, Monoclonal; D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D006023:Glycoproteins; D011518:Proto-Oncogene Proteins; C494957:FYN protein, human; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051076:Proto-Oncogene Proteins c-fyn