Viret C, He X, Janeway C A
Section of Immunobiology, Yale University School of Medicine, and Howard Hughes Medical Institute, New Haven, CT 06520-8011, USA.
Proc Natl Acad Sci U S A. 2001 Jul 31;98(16):9243-8. doi: 10.1073/pnas.161274698. Epub 2001 Jul 24.
The Y-Ae mAb and the 1H3.1 alphabeta T cell antigen receptor (TCR) are both specific for the I-Ealpha52-68 peptide bound to the I-A(b) major histocompatibility complex (MHC) class II molecule. Antigen-presenting cells (APCs) from I-A(b+) mice with a natural or transgenic (Tg) I-Ealpha chain activate mature 1H3.1 T cells and cause the deletion of 1H3.1 TCR Tg thymocytes. However, 1H3.1 T cells were neither activated nor inactivated by confrontation with APCs from I-Ab-Ep mice in which I-A(b) molecules are occupied only by the covalently associated Ealpha52-68 peptide. Instead, immature 1H3.1 TCR Tg thymocytes were efficiently positively selected into the CD4 lineage in the I-Ab-Ep thymus. This selection relied on specific recognition of the Ealpha52-68/I-A(b) complex because it was blocked by Y-Ae. 1H3.1 TCR Tg T cells maturing in the I-Ab-Ep thymus efficiently populated the periphery, displayed a naive phenotype, and were specifically reactive to the Ealpha52-68 peptide or to I-A(b+)I-Ealpha(+) APCs, indicating that 1H3.1 T cells were not antagonized in I-Ab-Ep mice. The data identify major histocompatibility complex class II molecules with only a covalently attached self-peptide as a ligand for in vivo positive selection of T cells specific for the same peptide.
Y-Ae单克隆抗体和1H3.1αβT细胞抗原受体（TCR）都对与I-A(b)主要组织相容性复合体（MHC）II类分子结合的I-Eα52-68肽具有特异性。来自具有天然或转基因（Tg）I-Eα链的I-A(b+)小鼠的抗原呈递细胞（APC）激活成熟的1H3.1 T细胞，并导致1H3.1 TCR转基因胸腺细胞的缺失。然而，当与I-Ab-Ep小鼠的APC接触时，1H3.1 T细胞既未被激活也未被灭活，在I-Ab-Ep小鼠中，I-A(b)分子仅被共价结合的Eα52-68肽占据。相反，未成熟的1H3.1 TCR转基因胸腺细胞在I-Ab-Ep胸腺中被有效地阳性选择进入CD4谱系。这种选择依赖于对Eα52-68/I-A(b)复合物的特异性识别，因为它被Y-Ae阻断。在I-Ab-Ep胸腺中成熟的1H3.1 TCR转基因T细胞有效地在外周组织中聚集，表现出幼稚表型，并对Eα52-68肽或I-A(b+)I-Eα(+) APC具有特异性反应，表明1H3.1 T细胞在I-Ab-Ep小鼠中未受到拮抗。这些数据确定了仅带有共价连接的自身肽的主要组织相容性复合体II类分子作为体内对相同肽具有特异性的T细胞阳性选择的配体。
