Distinct vascular lesions in giant cell arteritis share identical t cell clonotypes

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 Vβ1-Vβ20 revealed that all TCR Vβ 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 Vβ chains documented that individual TCR specificities were present in multiple copies, indicating clonal expansion. T cells with identical β chains were isolated from distinct inflammatory loci of the same patient. These specificities represented only a small fraction of tissue-infiltrating T cells and involved the Vβ5.3 gene segment in the two patients sharing the HLA-DRBI*0401 allele. The third complementarity determining region of clonally expanded TCR/3 chains was characterized by a duster 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.