Species-specific binding of CD4 to the beta 2 domain of major histocompatibility complex class II molecules.
Species-specific binding of CD4 to the beta 2 domain of major histocompatibility complex class II molecules.
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DOI：
10.1084/jem.175.4.925
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发表时间：
1992-04-01
期刊：
影响因子：
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通讯作者：
Hämmerling GJ
中科院分区：
文献类型：
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作者：
Vignali DA;Moreno J;Schiller D;Hämmerling GJ
在小鼠 (IA beta b) 和人类 (DR3 beta) II 类 β 链之间构建外显子改组结构，以研究 CD4 和主要组织相容性复合物 (MHC) II 类分子之间的相互作用位点，并确定是否涉及物种屏障。分别通过单克隆抗体和肽结合测定确定，总体结构和肽结合槽似乎不受外显子改组过程的影响。虽然纯化的 CD4+ BALB/c T 细胞在混合白细胞反应中对表达整个 IA 分子的转染子反应强烈，但对含有 DR beta 2 结构域的 IA 分子的反应大大降低。此外，DR中IAβ2结构域的存在未能恢复整个DR分子的弱异种反应性。对小鼠 HEL 特异性、IA α k β b 限制性 T 细胞杂交瘤也进行了类似的观察，与外显子改组的 IA 分子相比，其对整体的反应明显更强。 CD4 参与这些差异反应通过以下观察得到证实：CD4 丢失变体对两种分子的反应相当，并且将 CD4 转染到这些细胞中恢复了亲本表型。相比之下，用人 CD4 转染的 CD4 丢失变体对整个分子和外显子改组分子的反应相同。总而言之，这些数据暗示存在部分物种屏障，并表明除了其他接触位点外，CD4 还可能与 MHC II 类分子的 β2 结构域相互作用。提出了 CD4 与 MHC II 类分子相互作用的模型。
Exon-shuffled constructs between mouse (IA beta b) and human (DR3 beta) class II beta chains were made to study the interaction sites between CD4 and major histocompatibility complex (MHC) class II molecules, and to determine whether a species barrier is involved. The overall structure and the peptide binding groove appeared to be unaffected by the exon shuffling procedure as determined by monoclonal antibody and peptide binding assays, respectively. While purified CD4+ BALB/c T cells responded strongly in a mixed leukocyte reaction to transfectants expressing the whole IA molecule, the response to IA molecules containing a DR beta 2 domain was substantially reduced. In addition, the presence of an IA beta 2 domain in DR failed to restore the weak xenoreactivity to the whole DR molecule. Similar observations were made with murine HEL-specific, IA alpha k beta b-restricted T cell hybridomas which responded significantly stronger to the whole compared with the exon-shuffled IA molecules. The involvement of CD4 in these differential responses was confirmed by the observation that CD4 loss variants responded to both molecules comparably, and transfection of CD4 into these cells restored the parental phenotype. In contrast, CD4 loss variants transfected with human CD4 responded equally to both the whole and the exon-shuffled molecules. Taken together, these data imply the existence of a partial species barrier, and suggest that CD4 interacts with the beta 2 domain of MHC class II molecules, probably in addition to other contact sites. Models for the interaction of CD4 with MHC class II molecules are presented.