MUC1 mucin-mediated regulation of human T cells.
MUC1 mucin is expressed by normal human epithelial cells and is overproduced in underglycosylated form by malignant epithelial cells. A number of anticancer immunotherapeutic strategies are being designed with the goal of inducing humoral and cellular immune responses against MUC1 mucin. Newly synthesized MUC1 mucin is also expressed on polyclonally stimulated human T cells. An immunoregulatory role has been postulated for MUC1 mucin expressed by activated T cells. We now show that several MUC1 peptide and glycopeptide epitope specific antibodies bind to activated T cells and inhibit their proliferation. Inhibition by antibody B27.29 could be reversed by glycopeptide haptens specific for the antibody. Intact antibody B27.29 and its divalent F(ab')(2) fragment inhibited the proliferation of T cells undergoing T cell activation but the monovalent Fab' fragment did not, indicating that cross-linking of the MUC1 antigen on T cells is required for the inhibitory effect. MUC1 expression on activated T cells was increased in the presence of IL-12 but was not affected by IFN-gamma, IL-2, IL-4, IL-5, IL-10, IL-13 or TNF-alpha. Treatment of T cells inhibited by monoclonal antibody (MAb) B27.29 with either IL-2 or costimulatory anti-CD28 antibody restored proliferation to a level equivalent to that of control cultures. These results provide further support for the hypothesis that the expression of MUC1 on the activated T cell surface is associated with the regulation of T cell responses.
Agrawal
Babita
B
611-Heritage Medical Research Centre, Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, T6G 2S2, Canada. bagrawal@ualberta.ca
Longenecker
B Michael
BM
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006020:Glycopeptides / Q000276:immunology; D006241:Haptens / Q000276:immunology; D006801:Humans; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000276:immunology*; D018396:Mucin-1 / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D000099192:CD69 Antigens
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D006020:Glycopeptides; D006241:Haptens; D037181:Lectins, C-Type; D018396:Mucin-1; D015375:Receptors, Interleukin-2; D000099192:CD69 Antigens