HCMV triggers frequent and persistent UL40-specific unconventional HLA-E-restricted CD8 T-cell responses with potential autologous and allogeneic peptide recognition

• DOI: 10.1371/journal.ppat.1007041
• Publication Date: 2018-04-30T17:36:01Z
• Authors: Nicolas Jouand; Céline Bressollet...; Nathalie Gérard; Magali Giral; Pierrick Guérif; Audrey Rodallec; Romain Oger; Tiphaine Parrot; Mathilde Allard; Anne Cesbron-Gautier; Nadine Gervois; Béatrice Charreau
• Keywords: Adult; Male; QH301-705.5; Cytomegalovirus; [SDV.CAN]Life Sciences [q-bio]/Cancer; CD8-Positive T-Lymphocytes; Transplantation, Autologous; Viral Proteins; 03 medical and health sciences; 0302 clinical medicine; Humans; Biology (General); Cells, Cultured; Aged; Retrospective Studies; Antigen Presentation; Histocompatibility Antigens Class I; RC581-607; Middle Aged; Kidney Transplantation; Peptide Fragments; 3. Good health; Case-Control Studies; Cytomegalovirus Infections; Female; Immunologic diseases. Allergy; HLA-E Antigens; Research Article; T-Lymphocytes, Cytotoxic

Immune response against human cytomegalovirus (HCMV) includes a set of persistent cytotoxic NK and CD8 T cells devoted to eliminate infected prevent reactivation. HCMV antigens (pp65, IE1) presented by HLA class-I molecules are well characterized they associate with efficient virus control. HLA-E-restricted targeting UL40 signal peptides (HLA-EUL40) have recently emerged as non-conventional T-cell also observed in some hosts. The occurrence, specificity features HLA-EUL40 responses remain mostly unknown. Here, we detected quantified these blood samples from healthy donors (n = 25) kidney transplant recipients 121) investigated the biological determinants involved their occurrence. Longitudinal phenotype ex vivo analyses were performed comparison HLA-A*02/pp65-specific cells. Using 11 HLA-E/UL40 peptide tetramers demonstrated presence αβT up 32% seropositive HCMV+ hosts that may represent 38% total circulating T-cells at time point suggesting strong expansion post-infection. Host's HLA-A*02 allele, HLA-E *01:01/*01:03 genotype sequence infecting strain major factors affecting incidence These effector memory (CD45RAhighROlow, CCR7-, CD27-, CD28-) low level PD-1 expression. appear early post-infection display broad, unbiased, Vβ repertoire. Although induced strain-dependent, UL4015-23-specific manner, reactive toward broader nonapeptides varying 1-3 residues including most HLA-I peptides. Thus, induces life-long lasting potential allogeneic or/and autologous reactivity take place selectively least third infections according host concordance.