Processing of exogenous antigens for presentation by class I MHC molecules involves post-Golgi peptide exchange influenced by peptide-MHC complex stability and acidic pH
Processing of exogenous antigens for presentation by class I MHC molecules involves post-Golgi peptide exchange influenced by peptide-MHC complex stability and acidic pH
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DOI：
10.4049/jimmunol.167.3.1274
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发表时间：
2001-08-01
影响因子：
4.4
通讯作者：
Harding, CV
中科院分区：
文献类型：
--
作者：
Chefalo, PJ;Harding, CV
液泡替代 I 类 MHC (MHC-1) Ag 加工允许 MHC-I 分子呈递外源 Ag，同时抗原肽与高尔基体后 MHC-I 分子结合。我们研究了先前结合的肽及其解离在产生肽受体 MHC-I 分子中的作用。 TAP1 敲除巨噬细胞与初始外源肽一起孵育过夜，产生大量肽-K-b 复合物，可以影响随后的肽解离/交换。与 FAPGNYPAL、KVVRFDKL 或 RGYVYQGL 的初始孵育增强而不是减少随后读出肽（SIINFEKL 或 FAPGNYPAL）与 T 细胞的结合和呈递。因此，K-b分子可以通过初始（稳定）肽来稳定，增强它们结合读出肽并涉及肽解离/交换的能力。相反，与 SIINFEKL 作为稳定肽一起孵育减少了读出肽的呈递。 SIINFEKL-K-b 复合物比其他肽-K-b 复合物更稳定，这可能限制了它们对肽交换的贡献。稳定肽（FAPGNYPAL、KVVRFDKL 或 RGYVYQGL）增强了 HB101.Cri-OVA（表达 OVA 融合蛋白的大肠杆菌）的交替 MHC-I 加工，表明交替 MHC-1 Ag 加工涉及肽解离/交换。稳定肽比外源 OVA 肽 (SIINFEKL) 的呈递更能增强 HB101.Crl-OVA 的加工，表明在酸性吞噬体加工环境中可能会增强肽解离/交换。此外，将细胞暴露于酸性 pH 值会增加读出肽随后的结合和呈递。因此，肽解离/交换有助于交替 MHC-1 Ag 加工，并且可能受到肽-MHC-1 复合物稳定性和 pH 的影响。
Vacuolar alternate class I MHC (MHC-1) Ag processing allows presentation of exogenous Ag by MHC-I molecules with binding of antigenic peptides to post-Golgi MHC-I molecules. We investigated the role of previously bound peptides and their dissociation in generating peptide-receptive MHC-I molecules. TAP1-knockout macrophages were incubated overnight with an initial exogenous peptide, producing a large cohort of peptide-K-b complexes that could influence subsequent peptide dissociation/exchange. Initial incubation with FAPGNYPAL, KVVRFDKL, or RGYVYQGL enhanced rather than reduced subsequent binding and presentation of a readout peptide (SIINFEKL or FAPGNYPAL) to T cells. Thus, K-b molecules may be stabilized by an initial (stabilizing) peptide, enhancing their ability to bind readout peptide and implicating peptide dissociation/exchange. In contrast, incubation with SIINFEKL as stabilizing peptide reduced presentation of readout peptide. SIINFEKL-K-b complexes were more stable than other peptide-K-b complexes, which may limit their contribution to peptide exchange. Stabilizing peptides (FAPGNYPAL, KVVRFDKL, or RGYVYQGL) enhanced alternate MHC-I processing of HB101.Cri-OVA (Escherichia coli expressing an OVA fusion protein), indicating that alternate MHC-1 Ag processing involves peptide dissociation/exchange. Stabilizing peptide enhanced processing of HB101.Crl-OVA more than presentation of exogenous OVA peptide (SIINFEKL), suggesting that peptide dissociation/exchange may be enhanced in the acidic phagosomal processing environment. Furthermore, exposure of cells to acidic pH increased subsequent binding and presentation of readout peptide. Thus, peptide dissociation/ exchange contributes to alternate MHC-1 Ag processing and may be influenced by both stability of peptide-MHC-1 complexes and pH.