Regulation and trafficking of the HLA‐E molecules during monocyte‐macrophage differentiation

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: human leukocyte antigen‐;    E;    NK cells;    monocytic;   

DOI  :  10.1189/jlb.1A0415-172R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

HLA‐EisanonclassicalHLA‐classImoleculewhosebestknownroleistoprotectfromthenaturalkillercells.Morerecently,anadditionalfunctionmoresimilartothatofclassicalHLA‐classImolecules,i.e.,antigenpresentationtoTcells,isemerging.However,muchremainstobeexploredabouttheintracellulartraffickingoftheHLA‐Emolecules.Withtheuseof3differentcellularcontexts,2monocyticcelllines,U937andTHP1,andperipheralbloodmonocytes,weshowherearemarkableincreaseofHLA‐Eduringmonocyte‐macrophagedifferentiation.ThisgoesindependentlyfromtheclassicalHLA‐classI,themainsourceofHLA‐E‐specificpeptides,whichisfoundstronglyup‐regulatedupondifferentiationofperipheralbloodmonocytesbutnotatallinthecaseofU937andTHP1celllines.Althoughinallcases,therewasamoderateincreaseofHLA‐Eexpressedinthecellsurface,lysisbynaturalkillercellsiscomparablyrestoredbyananti‐NKG2AantibodyinuntreatedaswellasinPMA‐differentiatedU937cells.Instead,thegreatmajorityoftheHLA‐Eisretainedinthevesiclesoftheautophagy‐lysosomenetwork,wheretheycolocalizewiththemicrotubule‐associatedproteinlightchain3,aswellaswiththelysosomal‐associatedmembraneprotein1.WeconcludethatdifferentlyfromtheclassicalHLA‐classImolecules,theprimarydestinationofthenewlysynthesizedHLA‐Emoleculesinmacrophagesis,ratherthanthecellmembrane,theintracellularautophagy‐lysosomalvesicleswheretheyarestoredandwheretheycanencountertheexogenousantigens...

【 授权许可】

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