title: CD2/LFA-3 or LFA-1/ICAM-1 but not CD28/B7 interactions can augment cytotoxicity by virus-specific CD8+ cytotoxic T lymphocytes.
abstract: It is well established that adhesion molecules are required for interaction between cytotoxic T lymphocytes (CTL) and target cells. Two adhesion pathways, CD2/LFA-3 and LFA-1/ICAM-1 can support cytotoxicity by allospecific CD8+ CTL. In this study, it was investigated whether these adhesion pathways can be utilized independently by influenza virus-specific HLA-A2-restricted CTL clones. It was furthermore examined whether the CD28/B7 pathway can augment virus-specific CTL activity. To this end, seven CD8+ CTL clones were established that were specific for a peptide encompassing positions 59 to 68 (p[59-68]) of the influenza virus matrix protein. These seven clones apparently originated from different precursors, as they utilized different V alpha and V beta or J alpha gene segments. Six of seven clones were able to lyse mouse L cells co-transfected with HLA-A2 and either LFA-3 (LA2/LFA-3) or ICAM-1 (LA2/ICAM-1) in the presence of p[59-68] but did not lyse L cells that expressed only HLA-A2 and peptide. Three of the most cytotoxic clones were selected for further analysis. The cytotoxicity of the clones against LA2/LFA-3 cells was blocked by anti-LFA-3 and anti-CD2 monoclonal antibodies (mAb), while these antibodies did not affect cytotoxicity against LA2/ICAM-1 cells. Likewise, the activity against LA2/ICAM-1 was blocked only by anti-LFA-1 and ICAM-1 mAb. These clones were unable to lyse L cells co-transfected with HLA-A2 and B7, the counter structure of CD28, despite the fact that these clones expressed CD28. These data indicate that CD8+ virus-specific CTL can utilize either the CD2/LFA-3 or the LFA-1/ICAM-1 adhesion pathway. The CD28/B7 pathway seems not to be required for cytotoxicity mediated by activated virus-specific CTL.
authors.affiliation: DNAX Research Institute, Palo Alto, CA 94304-1104.
authors.forename: R
authors.initials: R
authors.lastname: de Waal Malefyt
authors.forename: S
authors.initials: S
authors.lastname: Verma
authors.forename: M T
authors.initials: MT
authors.lastname: Bejarano
authors.forename: M
authors.initials: M
authors.lastname: Ranes-Goldberg
authors.forename: M
authors.initials: M
authors.lastname: Hill
authors.forename: H
authors.initials: H
authors.lastname: Spits
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D001483:Base Sequence; D018801:CD2 Antigens; D018106:CD28 Antigens; D018968:CD58 Antigens; D015815:Cell Adhesion Molecules / Q000276:immunology; D002460:Cell Line; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D011971:Receptors, Immunologic / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014162:Transfection; D014763:Viral Matrix Proteins / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D018106:CD28 Antigens; D018968:CD58 Antigens; D015815:Cell Adhesion Molecules; D015789:HLA-A2 Antigen; D016169:Lymphocyte Function-Associated Antigen-1; C031540:M-protein, influenza virus; D008562:Membrane Glycoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011971:Receptors, Immunologic; D014763:Viral Matrix Proteins; D018799:Intercellular Adhesion Molecule-1