Yu Wong, Jiang Ning, Ebert Peter J R, Kidd Brian A, Müller Sabina, Lund Peder J, Juang Jeremy, Adachi Keishi, Tse Tiffany, Birnbaum Michael E, Newell Evan W, Wilson Darrell M, Grotenbreg Gijsbert M, Valitutti Salvatore, Quake Stephen R, Davis Mark M
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA; Division of Hematology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Department of Bioengineering, Stanford University School of Medicine, Stanford, CA 94305, USA.
Immunity. 2015 May 19;42(5):929-41. doi: 10.1016/j.immuni.2015.05.001.
It has long been thought that clonal deletion efficiently removes almost all self-specific T cells from the peripheral repertoire. We found that self-peptide MHC-specific CD8(+) T cells in the blood of healthy humans were present in frequencies similar to those specific for non-self antigens. For the Y chromosome-encoded SMCY antigen, self-specific T cells exhibited only a 3-fold lower average frequency in males versus females and were anergic with respect to peptide activation, although this inhibition could be overcome by a stronger stimulus. We conclude that clonal deletion prunes but does not eliminate self-specific T cells and suggest that to do so would create holes in the repertoire that pathogens could readily exploit. In support of this hypothesis, we detected T cells specific for all 20 amino acid variants at the p5 position of a hepatitis C virus epitope in a random group of blood donors.
长期以来，人们一直认为克隆清除能有效地从外周库中去除几乎所有自身特异性T细胞。我们发现，健康人类血液中自身肽MHC特异性CD8(+) T细胞的频率与非自身抗原特异性T细胞的频率相似。对于Y染色体编码的SMCY抗原，自身特异性T细胞在男性中的平均频率仅比女性低3倍，并且对肽激活呈无反应状态，尽管这种抑制可以通过更强的刺激来克服。我们得出结论，克隆清除会修剪但不会消除自身特异性T细胞，并表明这样做会在库中产生病原体很容易利用的漏洞。为支持这一假设，我们在一组随机的献血者中检测到了针对丙型肝炎病毒表位p5位置上所有20种氨基酸变体的T细胞。
