Kloetzel Peter Michael, Ossendorp Ferry
Institut für Biochemie, Charité-Medizinische Fakultät der Humboldt Universität zu Berlin, Monbijoustrasse 2, 10117 Berlin, Germany.
Curr Opin Immunol. 2004 Feb;16(1):76-81. doi: 10.1016/j.coi.2003.11.004.
MHC-class-I-presented peptides are predominantly generated by the proteasome system. IFN-gamma strongly influences the processing efficiency by inducing immunoproteasome formation and proteasome activator PA28 synthesis. Depending on the protein substrate, the presence of immunoproteasomes and PA28 influence epitope liberation either positively or negatively. Abundantly occurring defective ribosomal products are a major source for proteasome-dependent antigen processing; however, antigen presentation is relatively inefficient. This is in part due to the existence of a panel of cytosolic aminopeptidases, such as bleomycin hydrolase (BH), puromycin-sensitive aminopeptidase (PSA) and thimet oligoendopeptidase (TOP), that can destroy epitopes or their precursors. Other aminopeptidases, such as leucine aminopeptidase (LAP) and endoplasmic reticulum aminopeptidase 1 (ERAP 1), can trim epitope precursors from the amino terminus to their correct size for MHC class I binding to enhance antigen presentation. Recent evidence suggests that tripeptidyl peptidase II (TPPII), a large peptidase with exo-and endo-proteolytic activities, is also involved in antigen processing and may generate a specific set of MHC class I epitopes.
主要组织相容性复合体I类（MHC-I）呈递的肽主要由蛋白酶体系统产生。γ干扰素通过诱导免疫蛋白酶体形成和蛋白酶体激活剂PA28的合成，强烈影响加工效率。根据蛋白质底物的不同，免疫蛋白酶体和PA28的存在对表位释放的影响可能是正向的，也可能是负向的。大量存在的缺陷核糖体产物是蛋白酶体依赖性抗原加工的主要来源；然而，抗原呈递效率相对较低。这部分是由于存在一组胞质氨基肽酶，如博来霉素水解酶（BH）、嘌呤霉素敏感氨基肽酶（PSA）和硫醚寡肽酶（TOP），它们可以破坏表位或其前体。其他氨基肽酶，如亮氨酸氨基肽酶（LAP）和内质网氨基肽酶1（ERAP 1），可以从氨基末端将表位前体修剪至与MHC I类结合的正确大小，以增强抗原呈递。最近的证据表明，三肽基肽酶II（TPPII），一种具有外切和内切蛋白水解活性的大型肽酶，也参与抗原加工，并可能产生一组特定的MHC I类表位。
