Theoretical Biology and Bioinformatics, Utrecht University, 3584 CH Utrecht, The Netherlands.
J Immunol. 2013 Jun 1;190(11):5454-8. doi: 10.4049/jimmunol.1203569. Epub 2013 Apr 19.
It was recently shown that the expansion of CD4(+) T cells during a primary immune reaction to a peptide from cytochrome c decreases ~0.5 log for every log increase in the number of cognate precursor cells, and that this remains valid over more than four orders of magnitude (Quiel et al. 2011. Proc. Natl. Acad. Sci. USA. 108: 3312-3317). This observed "power law" was explained by a mechanism where nondividing mature T cells inhibit the proliferation of less-differentiated cells of the same specificity. In this article, we interpret the same data by a mechanism where CD4(+) T cells acquire cognate peptide-MHC (pMHC) complexes from the surface of APCs, thereby increasing the loss rate of pMHC. We show that a mathematical model implementing this "T cell grazing" mechanism, and having a T cell proliferation rate that is determined by the concentration of pMHC, explains the data equally well. As a consequence, the data no longer unequivocally support the previous explanation, and the increased loss of pMHC complexes on APCs at high T cell densities is an equally valid interpretation of this striking data.
最近的研究表明，在针对细胞色素 c 肽的初次免疫反应中，CD4(+)T 细胞的扩增会随着同源前体细胞数量的每增加一个对数级而减少约 0.5 个对数级，并且这种情况在超过四个数量级的范围内仍然有效（Quiel 等人，2011. Proc. Natl. Acad. Sci. USA. 108: 3312-3317）。这种观察到的“幂律”现象可以用一种机制来解释，即非分裂的成熟 T 细胞抑制同一特异性的分化程度较低的细胞的增殖。在本文中，我们通过一种机制来解释相同的数据，即在这种机制中，CD4(+)T 细胞从 APC 的表面获取同源肽-MHC（pMHC）复合物，从而增加 pMHC 的丢失率。我们表明，一个实施这种“T 细胞放牧”机制的数学模型，并且具有由 pMHC 浓度决定的 T 细胞增殖率，同样可以很好地解释这些数据。因此，这些数据不再明确支持之前的解释，并且在高 T 细胞密度下 APC 上 pMHC 复合物的丢失增加是对这些引人注目的数据的同样有效的解释。
