title: Identification of T cells responding to a self-protein modified by an external agent.
abstract: An interesting class of immune responses is that in which an environmental agent modifies a self-protein. Heparin induced thrombocytopenia (HIT) is associated with an antibody response in which the immunogen is a self-protein, platelet factor 4 (PF4), modified by an external agent, heparin. We tested the hypothesis that a T cell component exists in HIT, which like the humoral response, also requires the combination of heparin and PF4 to be activated. We identify here, a subset of T cells derived from a subject with severe HIT, which were expanded preferentially in 14-day in vitro cultures specifically in the presence of PF4:heparin complexes. A combination of T cell receptor spectratyping, CDR3 sequencing, and clonotype-specific probe hybridization were used to identify the responding T cells. The three BV17 T cell "clonotypes" thus identified had a CDR3 length of 10 amino acids, used BJ1.2, and displayed a conserved CDR3 sequence motif. These T cells are an example of a cellular response to environmentally altered self and are likely to be directly involved in HIT by functioning as T helper cells. The results are discussed in terms of the possible role of modification of antigen presentation by the external agent in this response.
authors.affiliation: Blood Research Institute, Blood Center of SE Wisconsin, Milwaukee, USA.
authors.forename: S
authors.initials: S
authors.lastname: Bacsi
authors.forename: R
authors.initials: R
authors.lastname: Geoffrey
authors.forename: G
authors.initials: G
authors.lastname: Visentin
authors.forename: R
authors.initials: R
authors.lastname: De Palma
authors.forename: R
authors.initials: R
authors.lastname: Aster
authors.forename: J
authors.initials: J
authors.lastname: Gorski
mesh_terms: D000368:Aged; D020816:Amino Acid Motifs; D001324:Autoantigens / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D002999:Clone Cells; D003001:Cloning, Molecular; D004306:Dose-Response Relationship, Immunologic; D004357:Drug Synergism; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis; D006493:Heparin / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D018655:Lymphocyte Count; D008297:Male; D005810:Multigene Family / Q000276:immunology; D010978:Platelet Factor 4 / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000737:chemistry; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D015203:Reproducibility of Results; D013234:Stem Cells / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013921:Thrombocytopenia / Q000139:chemically induced / Q000276:immunology
chemical_list: D001324:Autoantigens; D018984:Epitopes, T-Lymphocyte; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D010978:Platelet Factor 4; D006493:Heparin