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Blood, 15 February 2008, Vol. 111, No. 4, pp. 2053-2061.
Prepublished online as a Blood First Edition Paper on November 6, 2007; DOI 10.1182/blood-2007-04-079863.
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Submitted April 4, 2007
Accepted October 12, 2007
CD4+ T cells specific for glycoprotein B from cytomegalovirus exhibit extreme conservation of T cell receptor usage between different individuals
Laura Crompton, Naeem Khan, Rajiv Khanna, Laxman Nayak, and Paul A. H. Moss*
CRUK Institute for Cancer Studies, University of Birmingham, Birmingham, United Kingdom
Division of Immunology, School of Infection & Host Defence, University of Liverpool, Liverpool, United Kingdom
Division of Infectious Diseases and Immunology, Queensland Institute Medical Research, Queensland, Australia
Department of Applied Gerontology, Selly Oak Hospital, Birmingham, United Kingdom
* Corresponding author; email: p.moss{at}bham.ac.uk.
Antigen-specific CD8+ cytotoxic T cells often demonstrate extreme conservation of T cell receptor usage between different individuals but similar characteristics have not been documented for CD4+ T cells. CD4+ T cells predominantly have a helper immune role but a cytotoxic CD4+ T cell subset has been characterised and we have studied the cytotoxic CD4+ T cell response to a peptide from human cytomegalovirus glycoprotein B presented through HLA-DRB*0701. We show that this peptide elicits a cytotoxic CD4+ T cell response which averages 3.6% of the total CD4+ T cell repertoire of CMV seropositive donors. Moreover CD4+ cytotoxic T cell clones isolated from different individuals exhibit extensive conservation of TCR usage which indicates strong T cell clonal selection for peptide recognition. Remarkably, this TCR sequence was recently reported in over 50% of cases of CD4+ T cell large granular lymphocytosis. Immunodominance of cytotoxic CD4+ T cells thus parallels that of CD8+ subsets and suggests that cytotoxic effector function is critical to the development of T cell clonal selection, possibly from immune competition secondary to lysis of antigen presenting cells. In addition these TCR sequences are highly homologous to those observed in HLA-DR7+ patients with CD4+ T cell large granular lymphocytosis and implicate cytomegalovirus as a likely antigenic stimulus for this disorder.
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