Sekimata M, Tanabe M, Sarai A, Yamamoto J, Kariyone A, Nakauchi H, Egawa K, Takiguchi M
Department of Tumor Biology, University of Tokyo, Japan.
J Immunol. 1993 May 15;150(10):4416-26.
Previous studies indicated that weak xenoresponse to HLA class I by mouse T cells is due to the inefficient interaction of mouse CD8 with the alpha 3 domain of HLA class I. The present study using chimeric H-2Kb molecules with recombinant alpha 3 domain between H-2Kb and HLA-B7 as well as single amino acid mutants of H-2Kb demonstrated that each substitution at residues 224 and 228 affects recognition of CD8-dependent mouse CTL clones. On the other hand, reactivity of IL-2-producing H-2Kb-specific T cell hybridoma transfected with mouse CD8 alpha was abrogated by substitution at residue 224 but not by that at residue 228. This indicates that the substitution at residue 228 affects recognition of CD8-dependent CTL but does not critically affect binding of CD8 to MHC class I molecules, although residue 224 abrogates binding of CD8. The model structure of the alpha 3 domain of H-2Kb suggests that the substitution at residue 224 induces conformational change of CD8 binding loop, whereas minimum structure change by the substitution at residue 228 is expected. It is therefore speculated that minimum structure change of CD8 binding loop by substitution at residue 228 may influence binding affinity of CD8, which abrogates recognition of CD8-dependent CTL but not IL-2 production of the CD8-dependent T cell hybridoma.
先前的研究表明，小鼠T细胞对HLA I类分子的异种反应较弱，是由于小鼠CD8与HLA I类分子的α3结构域之间的相互作用效率低下。本研究使用在H-2Kb和HLA-B7之间具有重组α3结构域的嵌合H-2Kb分子以及H-2Kb的单氨基酸突变体，证明在第224和228位残基处的每一次取代都会影响CD8依赖性小鼠CTL克隆的识别。另一方面，转染了小鼠CD8α的产生IL-2的H-2Kb特异性T细胞杂交瘤的反应性在第224位残基处被取代所消除，但在第228位残基处被取代则没有。这表明第228位残基处的取代影响CD8依赖性CTL的识别，但对CD8与MHC I类分子的结合没有关键影响，尽管第224位残基消除了CD8的结合。H-2Kb的α3结构域的模型结构表明，第224位残基处的取代诱导了CD8结合环的构象变化，而预计第228位残基处的取代引起的结构变化最小。因此推测，第228位残基处的取代导致CD8结合环的结构变化最小，可能会影响CD8的结合亲和力，这消除了对CD8依赖性CTL的识别，但不会影响CD8依赖性T细胞杂交瘤的IL-2产生。
