Maurice M M, Gould D S, Carroll J, Vugmeyster Y, Ploegh H L
Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7437-42. doi: 10.1073/pnas.141143298. Epub 2001 Jun 12.
The H-2Ld alloreactive 2C T cell receptor (TCR) is commonly considered as being positively selected on the H-2Kb molecule. Surprisingly, 2C TCR+ CD8+ single-positive T cells emerge in massive numbers in fetal thymic organ culture originating from 2C transgenic, H-2KbD(b-/-) (2C+KbD(b-/-)) but not in fetal thymic organ culture from beta2-microglobulin(-/-) 2C transgenic animals. Mature CD8+ T cells are observed in newborn but not in adult 2C+KbD(b-/-) mice. These CD8+ T cells express the alpha4beta7 integrin, which allows them to populate the intestine, a pattern of migration visualized by intrathymic injection of FITC and subsequent accrual of FITC-labeled lymphocytes in the gut. We conclude that the 2C TCR is reactive not only with H-2Ld and H-2Kb, but also with nonclassical MHC class I products to enable positive selection of 2C+ T cells in the fetal and newborn thymus and to support their maintenance in the intestine.
H-2Ld同种异体反应性2C T细胞受体(TCR)通常被认为是在H-2Kb分子上进行阳性选择的。令人惊讶的是,在源自2C转基因、H-2KbD(b-/-)(2C+KbD(b-/-))的胎儿胸腺器官培养物中,大量出现2C TCR+ CD8+单阳性T细胞,而在β2-微球蛋白(-/-) 2C转基因动物的胎儿胸腺器官培养物中则未出现。在新生的2C+KbD(b-/-)小鼠中观察到成熟的CD8+ T细胞,但在成年小鼠中未观察到。这些CD8+ T细胞表达α4β7整合素,这使它们能够在肠道中聚集,通过胸腺内注射异硫氰酸荧光素(FITC)以及随后在肠道中出现FITC标记的淋巴细胞来观察这种迁移模式。我们得出结论,2C TCR不仅与H-2Ld和H-2Kb反应,还与非经典MHC I类产物反应,从而在胎儿和新生胸腺中实现2C+ T细胞的阳性选择,并支持它们在肠道中的维持。