Kawasaki H, Becker M L, Hedrick S M
Department of Biology, University of California, San Diego, La Jolla 92093-0063.
New Biol. 1991 May;3(5):487-97.
A chimeric T-cell receptor (TCR) alpha-chain gene was produced by shuffling the immunoglobulin VDJH from a 40-140 digoxin-specific hybridoma onto alpha-chain constant region (C alpha) exons. This hybrid immunoglobulin-TCR gene was used to produce transgenic mice. Previous results indicated that this chimeric gene encoded a polypeptide that associated with endogenously encoded beta chains to form a hybrid TCR. T cells expressing this receptor could be stimulated with antibodies specific for CD3 or the 40-140 idiotype (Id40-140), and also with digoxin coupled to bovine serum albumin (digoxin-BSA). We were interested in determining whether a hybrid receptor such as this could also recognize the natural ligand of T cells, namely allelic variants of major histocompatibility complex (MHC) molecules. A T-cell hybridoma was produced that expressed a hybrid receptor with specificity for an IAk-encoded determinant, digoxin-BSA, or staphyloccocal enterotoxin B. Transfection experiments showed that the specificity for MHC determinants was dependent on both the hybrid alpha chain and a particular beta chain. These results indicate that a V beta domain combined with a VH domain can produce a receptor capable of reacting with MHC molecules, and at the same time retain specificities mediated by the beta chain and alpha chain alone. A conclusion is that the pervasive MHC specificity of the TCR is not unique to the family of TCR heterodimers, but is selected, and can be mediated by immunoglobulin domains.
通过将来自一株40 - 140地高辛特异性杂交瘤的免疫球蛋白VDJH重排到α链恒定区（Cα）外显子上，构建了一个嵌合型T细胞受体（TCR）α链基因。该杂交免疫球蛋白 - TCR基因被用于制备转基因小鼠。先前的结果表明，这个嵌合基因编码一种多肽，它能与内源性编码的β链结合形成杂合TCR。表达这种受体的T细胞可以被针对CD3或40 - 140独特型（Id40 - 140）的抗体刺激，也能被偶联牛血清白蛋白的地高辛（地高辛 - BSA）刺激。我们感兴趣的是确定这样一种杂合受体是否也能识别T细胞的天然配体，即主要组织相容性复合体（MHC）分子的等位基因变体。制备了一个表达对IAk编码的决定簇、地高辛 - BSA或葡萄球菌肠毒素B具有特异性的杂合受体的T细胞杂交瘤。转染实验表明，对MHC决定簇的特异性依赖于杂合α链和特定的β链。这些结果表明，一个Vβ结构域与一个VH结构域结合可以产生一个能够与MHC分子反应的受体，同时单独保留由β链和α链介导的特异性。由此得出的结论是，TCR普遍存在的MHC特异性并非TCR异二聚体家族所特有，而是被选择的，并且可以由免疫球蛋白结构域介导。
