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Cryptic translation in immune survei...

University of California, Berkeley.

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Cryptic translation in immune surveillance under stress.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Cryptic translation in immune surveillance under stress./
作者:	Ow, Yongkai.
面頁冊數:	231 p.
附註:	Adviser: Nilabh Shastri.
Contained By:	Dissertation Abstracts International69-10B.
標題:	Biology, Molecular. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3331741
ISBN:	9780549831297

Cryptic translation in immune surveillance under stress.
Ow, Yongkai.

Cryptic translation in immune surveillance under stress. - 231 p.

Adviser: Nilabh Shastri.

Thesis (Ph.D.)--University of California, Berkeley, 2008.

The adaptive immune system relies heavily upon immune surveillance by CD8+ T cells to sense intracellular pathogens. Circulating CD8+ T cells carry out immune surveillance by scanning a library of peptides presented on MHC I (pMHC I) on the surface of most nucleated cells. Effective immune surveillance depends on the generation of a peptide library that constitutes a diverse and comprehensive representation of the intracellular protein milieu. The repertoire of peptides can be expanded by initiating translation of mRNA not only at the canonical AUG but also at non-AUG codons. We observe two types of translation initiation at non-AUG codons: wobble translation which follows the rules of conventional translation, and cryptic translation which invokes a novel mechanism of initiation. The biological significance and the mechanism of cryptic translation are unclear, although a previous model of cryptic translation has shown that an antigenic peptide from cryptic translation can elicit normal immune responses, and thus may contribute to the peptide repertoire. Here we show that cryptic pMHC I is enhanced when conventional AUG translation is inhibited by cellular stresses caused by ER overload and imbalance, nutrient deprivation, inflammatory stimuli and oxidative stress. A common theme that governs these stresses is that they inhibit global translation by inducing elF2alpha phosphorylation. Further investigation showed that generation of these cryptic pMHC I under stress conditions bypasses the normal controls of conventional translation in the elF2 pathway. This is because cryptic translation proceeds under conditions of limited ternary complex availability. Thus, cryptic translation uses a novel mechanism of initiation that is ternary complex independent for generating cryptic pMHCI under conditions of cellular stress, and hence may serve as a pMHC I surveillance mechanism of cellular stress.

ISBN: 9780549831297Subjects--Topical Terms:

1017719
Biology, Molecular.

Cryptic translation in immune surveillance under stress.
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520 $a The adaptive immune system relies heavily upon immune surveillance by CD8+ T cells to sense intracellular pathogens. Circulating CD8+ T cells carry out immune surveillance by scanning a library of peptides presented on MHC I (pMHC I) on the surface of most nucleated cells. Effective immune surveillance depends on the generation of a peptide library that constitutes a diverse and comprehensive representation of the intracellular protein milieu. The repertoire of peptides can be expanded by initiating translation of mRNA not only at the canonical AUG but also at non-AUG codons. We observe two types of translation initiation at non-AUG codons: wobble translation which follows the rules of conventional translation, and cryptic translation which invokes a novel mechanism of initiation. The biological significance and the mechanism of cryptic translation are unclear, although a previous model of cryptic translation has shown that an antigenic peptide from cryptic translation can elicit normal immune responses, and thus may contribute to the peptide repertoire. Here we show that cryptic pMHC I is enhanced when conventional AUG translation is inhibited by cellular stresses caused by ER overload and imbalance, nutrient deprivation, inflammatory stimuli and oxidative stress. A common theme that governs these stresses is that they inhibit global translation by inducing elF2alpha phosphorylation. Further investigation showed that generation of these cryptic pMHC I under stress conditions bypasses the normal controls of conventional translation in the elF2 pathway. This is because cryptic translation proceeds under conditions of limited ternary complex availability. Thus, cryptic translation uses a novel mechanism of initiation that is ternary complex independent for generating cryptic pMHCI under conditions of cellular stress, and hence may serve as a pMHC I surveillance mechanism of cellular stress.
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