Glas R, Franksson L, Ohlén C, Höglund P, Koller B, Ljunggren H G, Kärre K
Department of Tumor Biology, Karolinska Institutet, Stockholm, Sweden.
Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11381-5. doi: 10.1073/pnas.89.23.11381.
Cytotoxic T lymphocytes (CTLs) recognize major histocompatibility complex (MHC) class I molecules, normally composed of a heavy chain, a beta 2-microglobulin (beta 2m), and peptide antigens. beta 2m is considered essential for the assembly and intracellular transport of MHC class I molecules as well as their peptide presentation to CTLs. Contrary to this dogma, we now report the generation of allospecific and restricted CD8+ and TCR alpha beta+ CTLs (where TCR is T-cell receptor) capable of killing beta 2m-deficient cells. Such CTLs were obtained by priming mice with live allogeneic beta 2m- spleen cells or mutant lymphoma cells producing MHC class I protein but no detectable beta 2m. Although both beta 2m- and beta 2m-expressing lymphoma cells were rejected in allogeneic mice, only the former were efficient inducers of CTLs recognizing beta 2m- cells. These CTLs were MHC class I (H-2Kb or Db)-specific and CD8-dependent and did not require serum as a source of external beta 2m in the culture. They could be induced across major and minor histocompatibility barriers. The H-2-restricted CTLs generated in the latter case failed to kill the antigen-processing-deficient target RMA-S cells. The results show that MHC class I heavy chains in beta 2m- cells can be transported to the cell surface and act as antigens or antigen-presenting molecules to allospecific and MHC-restricted CTLs.
细胞毒性T淋巴细胞（CTLs）识别主要组织相容性复合体（MHC）I类分子，该分子通常由一条重链、一个β2-微球蛋白（β2m）和肽抗原组成。β2m被认为对于MHC I类分子的组装、细胞内运输以及它们向CTLs呈递肽至关重要。与这一传统观念相反，我们现在报告了能够杀伤β2m缺陷细胞的同种异体特异性且受限制的CD8⁺和TCR αβ⁺ CTLs（其中TCR是T细胞受体）的产生。此类CTLs是通过用活的同种异体β2m⁻脾细胞或产生MHC I类蛋白但无可检测到的β2m的突变淋巴瘤细胞对小鼠进行致敏而获得的。尽管β2m⁻和表达β2m的淋巴瘤细胞在同种异体小鼠中均被排斥，但只有前者是识别β2m⁻细胞的CTLs的有效诱导剂。这些CTLs是MHC I类（H-2Kb或Db）特异性的且依赖CD8，并且在培养中不需要血清作为外部β2m的来源。它们可以跨越主要和次要组织相容性屏障被诱导产生。在后一种情况下产生的H-2限制的CTLs无法杀伤抗原加工缺陷的靶细胞RMA-S细胞。结果表明，β2m⁻细胞中的MHC I类重链可以转运到细胞表面，并作为抗原或抗原呈递分子作用于同种异体特异性且MHC限制的CTLs。
