Invariant chain and DM edit self-peptide presentation by major histocompatibility complex (MHC) class II molecules.
Invariant chain and DM edit self-peptide presentation by major histocompatibility complex (MHC) class II molecules.
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DOI：
10.1084/jem.184.5.1747
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发表时间：
1996-11-01
期刊：
影响因子：
--
通讯作者：
Sant AJ
中科院分区：
文献类型：
--
作者：
Katz JF;Stebbins C;Appella E;Sant AJ
我们研究了不变链 (Ii) 和 DM 表达对主要组织相容性复合体 (MHC) II 类功能的影响。 Ii 在 II 类生物学中具有许多离散的功能，包括竞争性阻断内质网中的肽结合和增强内吞区室中的定位。 DM 被认为主要在内体中起作用，促进 Ii 衍生 (CLIP) 肽从 II 类抗原结合口袋解离以及随后的肽加载。在这项研究中，我们通过检查 Ii 和 DM 对大量同种异体反应性 T 细胞识别的表位表面表达的影响来评估 Ii 和 DM 的功能作用。我们发现大多数研究的表位都受到 Ii 和 DM 的影响。最引人注目的是，我们发现，APC 内的 DM 表达会消除而不是增强大部分 II 类肽复合物的表面表达。 DM 拮抗的表位似乎不是 CLIP 所特有的。最后，我们发现 DM 还能够消除对源自内部合成的 H-2Ld 蛋白的特定肽的识别。因此，DM 可能具有更广泛的功能，即编辑 II 类呈现的肽阵列，而不是主要用于去除 CLIP。这种编辑可以是正向的，也可以是负向的，这表明 DM 在呈递给 CD4 T 细胞的肽的展示中发挥着特定的作用。
We have studied the consequences of invariant chain (Ii) and DM expression on major histocompatibility complex (MHC) class II function. Ii has a number of discrete functions in the biology of class II, including competitive blocking of peptide binding in the endoplasmic reticulum and enhancing localization in the endocytic compartments. DM is thought to act primarily in endosomes to promote dissociation of the Ii-derived (CLIP) peptide from the class II antigen-binding pocket and subsequent peptide loading. In this study, we have evaluated the functional role of Ii and DM by examining their impact on surface expression of epitopes recognized by a large panel of alloreactive T cells. We find most epitopes studied are influenced by both Ii and DM. Most strikingly, we find that surface expression of a significant fraction of peptide-class II complexes is extinguished, rather than enhanced, by DM expression within the APC. The epitopes antagonized by DM do not appear to be specific for CLIP. Finally, we found that DM was also able to extinguish recognition of a defined peptide derived from the internally synthesized H-2Ld protein. Thus, rather than primarily serving in the removal of CLIP, DM may have a more generalized function of editing the array of peptides that are presented by class II. This editing can be either positive or negative, suggesting that DM plays a specifying role in the display of peptides presented to CD4 T cells.
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影响因子：
56.9
作者：
FungLeung, WP;Surh, CD;Karlsson, L
通讯作者：
Karlsson, L
影响因子：
3.7
作者：
IZUMI, M;MIYAZAWA, H;HANAOKA, F
通讯作者：
HANAOKA, F
影响因子：
64.5
作者：
BAKKE, O;DOBBERSTEIN, B
通讯作者：
DOBBERSTEIN, B
影响因子：
56.9
作者：
HUNT, DF;MICHEL, H;SETTE, A
通讯作者：
SETTE, A
DOI：
10.1084/jem.174.6.1607
发表时间：
1991-12-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Mellins E;Kempin S;Smith L;Monji T;Pious D
通讯作者：
Pious D