Ishizuka Jeffrey, Stewart-Jones Guillaume B E, van der Merwe Anton, Bell John I, McMichael Andrew J, Jones E Yvonne
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Immunity. 2008 Feb;28(2):171-82. doi: 10.1016/j.immuni.2007.12.018.
Immunodominant and public T cell receptor (TCR) usage is relatively common in many viral diseases yet surprising in the context of the large naive TCR repertoire. We examined the highly conserved Vbeta17:Valpha10.2 JM22 T cell response to the influenza matrix peptide (58-66)-HLA-A*0201 (HLA-A2-flu) through extensive kinetic, thermodynamic, and structural analyses. We found several conformational adjustments that accompany JM22-HLA-A2-flu binding and identified a binding "hotspot" within the Vbeta domain of the TCR. Within this hotspot, key germline-encoded CDR1 and CDR2 loop residues and a crucial but commonly coded residue in the hypervariable region of CDR3 provide the basis for the substantial bias in the selection of the germline-encoded Vbeta17 domain. The chances of having a substantial number of T cells in the naive repertoire that have HLA-A2-flu-specific Vbeta17 receptors may consequently be relatively high, thus explaining the immunodominant usage of this clonotype.
免疫显性和公共性T细胞受体（TCR）的使用在许多病毒性疾病中相对常见，但鉴于庞大的初始TCR库，这种情况令人惊讶。我们通过广泛的动力学、热力学和结构分析，研究了高度保守的Vβ17:Vα10.2 JM22 T细胞对流感病毒基质肽（58 - 66）-HLA - A*0201（HLA - A2 - 流感）的反应。我们发现了JM22与HLA - A2 - 流感结合时伴随的几种构象调整，并在TCR的Vβ结构域内确定了一个结合“热点”。在这个热点内，关键的种系编码CDR1和CDR2环残基以及CDR3高变区内一个关键但常见编码的残基，为种系编码Vβ17结构域选择中的显著偏差提供了基础。因此，初始库中大量具有HLA - A2 - 流感特异性Vβ17受体的T细胞出现的可能性可能相对较高，从而解释了这种克隆型的免疫显性使用情况。
