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Processing‐dependent and ‐independent pathways for recognition of iodinated contrast media by specific human T cells
Author(s) -
Keller M.,
Lerch M.,
Britschgi M.,
Tâche V.,
Gerber B. O.,
Lüthi M.,
Lochmatter P.,
Kanny G.,
Bircher A. J.,
Christiansen C.,
Pichler W. J.
Publication year - 2010
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/j.1365-2222.2009.03425.x
Subject(s) - antigen presenting cell , antigen , t cell receptor , antigen presentation , t cell , immunology , major histocompatibility complex , in vitro , stimulation , chemistry , microbiology and biotechnology , biology , immune system , endocrinology , biochemistry
Summary Background One to three percent of patients exposed to intravenously injected iodinated contrast media (CM) develop delayed hypersensitivity reactions. Positive patch test reactions, immunohistological findings, and CM‐specific proliferation of T cells in vitro suggest a pathogenetic role for T cells. We have previously demonstrated that CM‐specific T cell clones (TCCs) show a broad range of cross‐reactivity to different CM. However, the mechanism of specific CM recognition by T cell receptors (TCRs) has not been analysed so far. Objective To determine how T cells specifically recognize CM. Methods CM‐specific TCCs were generated from human blood of three CM‐allergic patients and a specific TCR was transfected into a mouse T cell hybridoma. Functional analysis such as proliferation assays, IL‐2 secretion assays, and calcium influx experiments were performed using irradiated, glutaraldehyde‐fixed, CM‐pre‐incubated, human leucocyte antigen (HLA)‐DR‐matched or ‐mismatched antigen‐presenting cells (APCs), and HLA‐blocking antibodies. Results We identified two mechanisms of T cell stimulation: some TCCs and the transfectant reacted to CM independent of uptake by APCs because proliferation/IL‐2 secretion occurred in the presence of glutaraldehyde‐fixed APCs, and intracellular calcium increased within seconds after drug addition. Other TCCs required functional APCs, compatible with uptake and presentation of CM on MHC‐class II molecules, as implied by three findings: (1) glutaraldehyde fixation of APCs abrogated presentation; (2) CM could not be washed away from CM‐pre‐incubated APCs; and (3) the optimal pulsing time was 10–20 h. Because allogeneic, MHC‐matched, CM‐pulsed APCs could induce proliferative responses as well, the ability of CM uptake and presentation is not unique to APCs from patients with CM‐induced delayed hypersensitivity. Conclusion Our data suggest that CM may be stimulatory for T cells either by direct binding to the MHC–TCR complex or by binding after uptake and processing by APCs. This questions the assumed inert nature of CM. Cite this as : M. Keller, M. Lerch, M. Britschgi, V. Tâche, B. O. Gerber, M. Lüthiuthi, P. Lochmatter, G. Kanny, A. J. Bircher, C. Christiansen and W. J. Pichler, Clinical & Experimental Allergy , 2010 (40) 257–268.