title: A divalent human leukocyte antigen-B7 fusion-protein up-regulates CD25 and CD69 in alloreactive CD8+ T cells bypassing CD28 costimulation.
abstract: BACKGROUND
  T cells recognize major histocompatibility complex (MHC) molecules and their cryptic antigenic peptides on antigen-presenting cells and are generally triggered to proliferate, and when sufficient, co-stimulation is available. In soluble form, monomeric MHC molecules can induce apoptosis, anergy, or decreases of the T-cell receptor (TCR).
  
  
  METHODS
  A dimeric fusion protein of the human leukocyte antigens (HLA)-B7 was molecularly engineered and expressed in a B-cell line to allow secretion. Alloreactive T cells were generated according to the standard protocol.
  
  
  RESULTS
  A dimer of approximately 160 kD was obtained, affinity purified, and used to study T-cell interaction. In immobilized form, this protein efficiently stimulated alloreactive T cells to proliferate and produce interleukin (IL)-2 and interferon (IFN)-gamma in a concentration-dependent manner, up-regulating CD25 and CD69 expression. In contrast, the soluble fusion protein induced T-cell apoptosis.
  
  
  CONCLUSIONS
  The dichotomy in T-cell regulation by a divalent MHC fusion protein warrants the use of MHC multimers as custom-designed immune-regulatory molecules both in transplantation and autoimmune disease.
authors.affiliation: Institute of Anatomy, University of Kiel, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Rickert
authors.forename: Judith
authors.initials: J
authors.lastname: Welke
authors.forename: Dirk
authors.initials: D
authors.lastname: Behrens
authors.forename: Nicholas
authors.initials: N
authors.lastname: Zavazava
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D017209:Apoptosis; D001402:B-Lymphocytes; D018122:B7-1 Antigen / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D019281:Dimerization; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D037181:Lectins, C-Type; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection; D015854:Up-Regulation; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018122:B7-1 Antigen; D018819:Dipeptidyl Peptidase 4; D006680:HLA Antigens; D037181:Lectins, C-Type; D011993:Recombinant Fusion Proteins; D000099192:CD69 Antigens