Joyce S, Negishi I, Boesteanu A, DeSilva A D, Sharma P, Chorney M J, Loh D Y, Van Kaer L
Department of Microbiology & Immunology, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey 17033, USA.
J Exp Med. 1996 Oct 1;184(4):1579-84. doi: 10.1084/jem.184.4.1579.
Thymic selection of natural killer-1+ natural T cells that express alpha beta T cell receptors requires a conserved beta 2-microglobulin-associated molecule, presumably CD1d, displayed by CD4+8+ thymocytes. Here we demonstrate that positive selection of natural T cells occurs independent of transporters associated with antigen presentation-1 (TAP-1) function. Moreover, natural T cells in TAP-1o/o mice are numerically expanded. Several H-2 class Ib molecules function in a TAP-independent manner, suggesting that if expressed in TAP-1o/o thymocytes, they could play a role in natural T cell development. Of these class Ib molecules, H-2TL is expressed by TAP-1o/o thymocytes. Moreover, we find that thymi of TL+ mice congenic or transgenic for H-2T18 also have a numerically expanded natural T cell repertoire compared with TL- mice. This expansion, as in TAP-1o/o thymi, is evident in each of the limited T cell receptor V beta chains expressed by natural T cells, suggesting that TL and CD1d impact similar repertoires. Thus TL, in addition to CD1d, plays a role in natural T cell development.
表达αβ T细胞受体的自然杀伤1+自然T细胞的胸腺选择需要一种保守的与β2-微球蛋白相关的分子,推测为CD1d,由CD4+8+胸腺细胞呈递。在此我们证明,自然T细胞的阳性选择独立于与抗原呈递相关的转运体1(TAP-1)的功能而发生。此外,TAP-1基因敲除小鼠中的自然T细胞数量增加。几种H-2 Ib类分子以不依赖TAP的方式发挥作用,这表明如果在TAP-1基因敲除的胸腺细胞中表达,它们可能在自然T细胞发育中发挥作用。在这些Ib类分子中,H-2TL在TAP-1基因敲除的胸腺细胞中表达。此外,我们发现,与H-2T18基因座相同或转基因的TL+小鼠的胸腺与TL-小鼠相比,自然T细胞库数量也有所增加。与TAP-1基因敲除的胸腺一样,这种增加在自然T细胞表达的有限的T细胞受体Vβ链中均很明显,这表明TL和CD1d影响相似的细胞库。因此,除了CD1d外,TL在自然T细胞发育中也发挥作用。