Diment S, Shinde S
Michael Heidelberger Division of Immunology, New York University Medical Center, NY 10016.
J Immunol. 1995 Jan 15;154(2):530-5.
Recently, APCs expressing genes for the alpha- and beta-chains of MHC class II, but not other proteins encoded in the MHC class II locus, have been found to be defective in processing proteins by the MHC class II Ag presentation pathway. Ag presentation of hen egg OVA has been examined in one of these cell lines, T2.Ak. OVA was processed normally by T2.Ak when compared with OVA processed by T1.Ak, a cell line that expresses the MHC genes missing in T2.Ak. By contrast, native hen egg lysozyme (HEL) was not presented as Ag by T2.Ak, which is in agreement with earlier results. Digestion with thiol proteases is important for Ag processing of HEL. We therefore analyzed the expression of these enzymes in T1.Ak and T2.Ak by using a reagent that specifically radiolabels thiol proteases. In these experiments, the repertoire of proteases expressed in the microsomes of T1.Ak was found to be distinct from the repertoire expressed by T2.Ak. Finally, in in vitro digestion experiments, the group of thiol proteases active in T1.Ak microsomes digested HEL differently from the group identified in T2.Ak. These results provide evidence that the defect in Ag presentation that is encoded by MHC genes and manifests itself in defective processing of HEL is not absolute. Further, the mutation in T2.Ak coincides with altered activities of thiol proteases, a class of enzymes involved in processing exogenous Ags.
最近，人们发现，表达MHC II类分子α链和β链基因，但不表达MHC II类基因座中编码的其他蛋白质的抗原呈递细胞（APCs），在通过MHC II类抗原呈递途径加工蛋白质方面存在缺陷。已在其中一种细胞系T2.Ak中检测了鸡卵OVA的抗原呈递情况。与由T1.Ak加工的OVA相比，T2.Ak能正常加工OVA，T1.Ak是一种表达T2.Ak中缺失的MHC基因的细胞系。相比之下，天然鸡卵溶菌酶（HEL）不能被T2.Ak呈递为抗原，这与早期结果一致。用硫醇蛋白酶消化对于HEL的抗原加工很重要。因此，我们通过使用一种能特异性放射性标记硫醇蛋白酶的试剂，分析了这些酶在T1.Ak和T2.Ak中的表达情况。在这些实验中，发现T1.Ak微粒体中表达的蛋白酶谱与T2.Ak表达的蛋白酶谱不同。最后，在体外消化实验中，T1.Ak微粒体中具有活性的硫醇蛋白酶组对HEL的消化方式与在T2.Ak中鉴定出的蛋白酶组不同。这些结果证明，由MHC基因编码且表现为HEL加工缺陷的抗原呈递缺陷并非绝对的。此外，T2.Ak中的突变与硫醇蛋白酶活性的改变一致，硫醇蛋白酶是一类参与加工外源性抗原的酶。
