Cross-recognition of human alloantigen by cytomegalovirus glycoprotein-specific CD4+ cytotoxic T lymphocytes: implications for graft-versus-host disease.
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.
Elkington
Rebecca
R
Tumour Immunology Laboratory, Co-operative Cetnre for Vaccine Technology, Division of Immunology, Queensland Institute Medical Research, University of Queensland, Brisbane, Australia. .
Khanna
Rajiv
R
D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology*; D006801:Humans; D007519:Isoantigens / Q000032:analysis*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000956:Antigens, Viral; D006023:Glycoproteins; D007519:Isoantigens