通过结合HLA结合预测和蛋白酶体加工确定的人巨细胞病毒IE1的一个CTL表位是异基因干细胞移植后患者主要免疫反应的靶点。

A CTL epitope from human cytomegalovirus IE1 defined by combining prediction of HLA binding and proteasomal processing is the target of dominant immune responses in patients after allogeneic stem cell transplantation.

作者信息

Hebart Holger, Rauser Georg, Stevanovic Stefan, Haenle Claire, Nussbaum Alexander K, Meisner Christoph, Bissinger Alfred L, Tenzer Stefan, Jahn Gerhard, Loeffler Juergen, Rammensee Hans-Georg, Schild Hansjörg, Einsele Hermann

机构信息

Medizinische Klinik II, Institut für Zellbiologie, Eberhard-Karls-Universität Tübingen, Tübingen, Germany.

出版信息

Exp Hematol. 2003 Oct;31(10):966-73. doi: 10.1016/s0301-472x(03)00203-0.

DOI:10.1016/s0301-472x(03)00203-0

PMID:14550813

Abstract

OBJECTIVE AND METHODS

In an attempt to define HCMV IE1-derived, HLA-A(*)0201-restricted epitopes, an advanced computer-based epitope prediction combining HLA binding and proteasomal cleavages in silico was performed.

RESULTS

This prediction algorithm clearly confirmed VLEETSVML to be the most likely CTL epitope. By tetramer staining, HCMV pp65 NLVPMVATV-specific CD8(+) T cells were detectable in 18/24 HCMV seropositive HLA-A(*)0201-expressing individuals (median frequency 0.58%; range 0.1%-4.7%), and IE1 VLEETSVML-specific CD8(+) T cells in 5/24 (median frequency 2.1%; range 0.1%-4.3%), respectively (p<0.01). Also in recipients of an allogeneic SCT, VLEETSVML- and NLVPMVATV-specific CD8(+) T cells were detectable in comparable frequencies, but again the number of patients with detectable pp65-specific CD8(+) T cells was higher (p=0.014). In 4/15 individuals, all demonstrating IE1 VLEETSVML-specific CD8(+) T cells prior to peptide stimulation, VLEETSVML-specific T cell lines (purity of 42.6%-98.6% of all CD3(+)/CD8(+) T cells) were successfully generated after 2-4 weeks of culture using the IFN-gamma secretion assay.

CONCLUSION

In conclusion, this novel prediction strategy efficiently predicted an immunodominant viral T-cell epitope.

摘要

目的与方法

为了确定人巨细胞病毒（HCMV）IE1衍生的、HLA - A(*)0201限制性表位，我们进行了一种先进的基于计算机的表位预测，该预测在计算机模拟中结合了HLA结合和蛋白酶体切割。

结果

该预测算法明确证实VLEETSVML是最有可能的细胞毒性T淋巴细胞（CTL）表位。通过四聚体染色，在18/24例表达HLA - A(*)0201的HCMV血清阳性个体中可检测到HCMV pp65 NLVPMVATV特异性CD8(+) T细胞（中位频率0.58%；范围0.1% - 4.7%），以及在5/24例个体中可检测到IE1 VLEETSVML特异性CD8(+) T细胞（中位频率2.1%；范围0.1% - 4.3%），（p<0.01）。在同种异体造血干细胞移植（SCT）受者中，也可检测到频率相当的VLEETSVML和NLVPMVATV特异性CD8(+) T细胞，但同样，可检测到pp65特异性CD8(+) T细胞的患者数量更高（p = 0.014）。在15例个体中的4例中，所有个体在肽刺激前均显示IE1 VLEETSVML特异性CD8(+) T细胞，使用干扰素 - γ分泌测定法，在培养2 - 4周后成功产生了VLEETSVML特异性T细胞系（占所有CD3(+)/CD8(+) T细胞的纯度为42.6% - 98.6%）。