Cytomegalovirus-specific CD8(+) T cells targeting different HLA/peptide combinations correlate with protection but at different threshold frequencies.
Cytomegalovirus (CMV) causes significant morbidity and mortality in patients after haematopoietic stem cell transplantation (HSCT). Due to limitations of current antiviral therapies, alternative approaches, involving transfer of donor-derived CMV-specific CD8(+) T cells, have been considered. Levels of such cells correlating with protection against CMV infection and disease have only been reported in patients expressing HLA-A*0201 and HLA-B*0702. This is despite an increasing number of reports describing cells targeting CMV peptides presented by other human leucocyte antigens (HLAs). Considering several frequent HLA alleles, our findings suggest that HLA-A*2402/pp65 (341-349)- and HLA-B*3501/pp65 (123-131)-specific CD8+ T cells correlate with protection from CMV reactivation at significantly lower cell levels than HLA-A*0101/pp50 (245-253)- and HLAA* 0201/pp65 (495-503)-specific CD8+ T cells, both in HSCT recipients posttransplant and in healthy CMV seropositive volunteers. This may result from a differing efficiency of the responses restricted by the two sets of HLA alleles. These findings add to the knowledge of immunodominance and differences in antigen processing that are coordinated in individuals with different HLA alleles and have direct implications for therapy and monitoring in patients.
Giest
Sandra
S
Anthony Nolan Research Institute, London, UK. sandragiest-research@yahoo.de
Grace
Sarah
S
Senegaglia
Alexandra C
AC
Pasquini
Ricardo
R
Gonzalo-Daganzo
Rosa M
RM
Fernández
Manuel N
MN
Mackinnon
Stephen
S
Madrigal
J Alejandro
JA
Travers
Paul J
PJ
D000293:Adolescent; D000328:Adult; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D000998:Antiviral Agents / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000235:genetics / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D015774:Ganciclovir / Q000627:therapeutic use; D015234:HLA-A Antigens / Q000235:genetics; D015789:HLA-A2 Antigen; D015235:HLA-B Antigens / Q000235:genetics; D015793:HLA-B7 Antigen; D006402:Hematologic Diseases / Q000628:therapy / Q000821:virology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019562:Viral Load; D055815:Young Adult
D000956:Antigens, Viral; D000998:Antiviral Agents; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D015235:HLA-B Antigens; C477444:HLA-B*07:02 antigen; D015793:HLA-B7 Antigen; D015774:Ganciclovir