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 Blood, 1 February 2005, Vol. 105, No. 3, pp. 1362-1364.
Prepublished online as a Blood First Edition Paper on September 30, 2004; DOI 10.1182/blood-2004-07-2602.

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TRANSPLANTATION
Brief report

Cross-recognition of human alloantigen by cytomegalovirus glycoprotein-specific CD4+ cytotoxic T lymphocytes: implications for graft-versus-host disease

Rebecca Elkington, and Rajiv Khanna

From the Tumour Immunology Laboratory and Co-operative Centre for Vaccine Technology, Division of Infectious Diseases and Immunology, Queensland Institute of Medical Research, Joint Oncology Program, Department of Molecular and Cellular Pathology, University of Queensland, Brisbane, Australia.

Presence of the HLA-DR7 allele in patients who receive transplants has been proposed as a risk factor for human cytomegalovirus (HCMV)–associated complications; however, the precise mechanism of this increased risk remains unresolved. Here we show that HLA-DR7–restricted HCMV-specific CD4+ cytotoxic T lymphocytes (CTLs) can display an unusual dual specificity toward a glycoprotein-B (gB) epitope and the alloantigen HLA-DR4. However, no HLA-DR4–specific alloreactivity was observed when the gB-specific CTLs were generated from virus carriers expressing both HLA-DR7 and DR4 alleles. This most likely demonstrates the clonal inactivation of potentially self-reactive T cells in humans. Fine specificity analysis showed that gB-specific CTLs from HLA-DR7+/DR4- individuals displayed a distinct pattern of recognition when compared with CTLs from HLA-DR7+/DR4+ individuals, presumably evading an area of the epitope that mimics a structure presented on HLA-DR4. These data illustrate a possible mechanism for the clinical association between HCMV and graft-versus-host disease.


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