title: Distinct vascular lesions in giant cell arteritis share identical T cell clonotypes.
abstract: Giant cell arteritis (GCA) is a spontaneous vasculitic syndrome that specifically targets the walls of medium and large arteries. Vascular lesions are characterized by patchy granulomatous infiltrates composed of T cells, macrophages, histiocytes, and giant cells. To test the hypothesis that a locally residing antigen recruits T cells into the vessel walls, we have analyzed T cell receptor (TCR) molecules of tissue infiltrating T cells. A total of 638 CD4+ T cell clones were isolated from temporal artery specimens of three patients with GCA. Analysis of TCR molecules for the usage of V beta 1-V beta 20 revealed that all TCR V beta elements were represented, demonstrating that interleukin 2 (IL-2)-responsive T cells infiltrating the tissue are highly diverse. To detect expanded T cell specificities, we made use of the patchy character of the inflammatory disease and compared the TCR repertoire of T cells established from independent vasculitic foci of the same artery. Sequence analysis of TCR V beta chains documented that individual TCR specificities were present in multiple copies, indicating clonal expansion. T cells with identical beta chains were isolated from distinct inflammatory foci of the same patient. These specificities represented only a small fraction of tissue-infiltrating T cells and involved the V beta 5.3 gene segment in the two patients sharing the HLA-DRB1*0401 allele. The third complementarity determining region of clonally expanded TCR beta chains was characterized by a cluster of negatively and positively charged residues, suggesting that the juxtaposed antigenic peptide is charged. The sharing of identical T cell specificities by distinct and independent regions of the granulomatous inflammation suggests that these T cells are disease relevant and that their repertoire is strongly restricted. These data suggest that an antigen residing in the arterial wall is recognized by a small fraction of CD4+ T cells in the inflammatory process characteristic for GCA.
authors.affiliation: Division of Rheumatology, Mayo Clinic and Foundation, Rochester, Minnesota 55905.
authors.forename: C M
authors.initials: CM
authors.lastname: Weyand
authors.forename: J
authors.initials: J
authors.lastname: Schönberger
authors.forename: U
authors.initials: U
authors.lastname: Oppitz
authors.forename: N N
authors.initials: NN
authors.lastname: Hunder
authors.forename: K C
authors.initials: KC
authors.lastname: Hicok
authors.forename: J J
authors.initials: JJ
authors.lastname: Goronzy
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D017252:CD3 Complex / Q000032:analysis / Q000235:genetics*; D015704:CD4 Antigens / Q000032:analysis; D002999:Clone Cells; D013700:Giant Cell Arteritis / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D011110:Polymorphism, Genetic; D011948:Receptors, Antigen, T-Cell / Q000032:analysis*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D013699:Temporal Arteries / Q000276:immunology / Q000473:pathology
chemical_list: D017252:CD3 Complex; D015704:CD4 Antigens; D015345:Oligonucleotide Probes; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta