Details

Autor(en) / Beteiligte

• Braendstrup, Peter
• Mortensen, Bo Kok
• Justesen, Sune
• Osterby, Thomas
• Rasmussen, Michael
• Hansen, Andreas Martin
• Christiansen, Claus Bohn
• Hansen, Morten Bagge
• Nielsen, Morten
• Vindelov, Lars
• Buus, Soren
• Stryhn, Anette

Titel

Identification and HLA-tetramer-validation of human [CD4.sup.+] and [CD8.sup.+] T cell responses against HCMV proteins IE1 and IE2

Ist Teil von

• PloS one, 2014-04, Vol.9 (4)

Ort / Verlag

Public Library of Science

Erscheinungsjahr

2014

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Human cytomegalovirus (HCMV) is an important human pathogen. It is a leading cause of congenital infection and a leading infectious threat to recipients of solid organ transplants as well as of allogeneic hematopoietic cell transplants. Moreover, it has recently been suggested that HCMV may promote tumor development. Both [CD4.sup.+] and [CD8.sup.+] T cell responses are important for long-term control of the virus, and adoptive transfer of HCMV-specific T cells has led to protection from reactivation and HCMV disease. Identification of HCMV-specific T cell epitopes has primarily focused on [CD8.sup.+] T cell responses against the pp65 phosphoprotein. In this study, we have focused on [CD4.sup.+] and [CD8.sup.+] T cell responses against the immediate early 1 and 2 proteins (IE1 and IE2). Using overlapping peptides spanning the entire IE1 and IE2 sequences, peripheral blood mononuclear cells from 16 healthy, HLA-typed, donors were screened by ex vivo IFN-[gamma] ELISpot and in vitro intracellular cytokine secretion assays. The specificities of [CD4.sup.+] and [CD8.sup.+] T cell responses were identified and validated by HLA class II and I tetramers, respectively. Eighty-one [CD4.sup.+] and 44 [CD8.sup.+] T cell responses were identified representing at least seven different CD4 epitopes and 14 CD8 epitopes restricted by seven and 11 different HLA class II and I molecules, respectively, in total covering 91 and 98% of the Caucasian population, respectively. Presented in the context of several different HLA class II molecules, two epitope areas in IE1 and IE2 were recognized in about half of the analyzed donors. These data may be used to design a versatile anti-HCMV vaccine and/or immunotherapy strategy.