Promiscuous binding of invariant chain-derived CLIP peptide to distinct HLA-I molecules revealed in leukemic cells.

Antigen presentation by HLA class I (HLA-I) and HLA class II (HLA-II) complexes is achieved by proteins that are specific for their respective processing pathway. The invariant chain (Ii)-derived peptide CLIP is required for HLA-II-mediated antigen presentation by stabilizing HLA-II molecules before...

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Autores principales:	Marvin M van Luijn, Arjan A van de Loosdrecht, Margit H Lampen, Peter A van Veelen, Adri Zevenbergen, Michel G D Kester, Arnoud H de Ru, Gert J Ossenkoppele, Thorbald van Hall, S Marieke van Ham
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c4a5eb86be014846968ef1aa4463edb1
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spelling	oai:doaj.org-article:c4a5eb86be014846968ef1aa4463edb12021-11-18T07:20:50ZPromiscuous binding of invariant chain-derived CLIP peptide to distinct HLA-I molecules revealed in leukemic cells.1932-620310.1371/journal.pone.0034649https://doaj.org/article/c4a5eb86be014846968ef1aa4463edb12012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22563374/?tool=EBIhttps://doaj.org/toc/1932-6203Antigen presentation by HLA class I (HLA-I) and HLA class II (HLA-II) complexes is achieved by proteins that are specific for their respective processing pathway. The invariant chain (Ii)-derived peptide CLIP is required for HLA-II-mediated antigen presentation by stabilizing HLA-II molecules before antigen loading through transient and promiscuous binding to different HLA-II peptide grooves. Here, we demonstrate alternative binding of CLIP to surface HLA-I molecules on leukemic cells. In HLA-II-negative AML cells, we found plasma membrane display of the CLIP peptide. Silencing Ii in AML cells resulted in reduced HLA-I cell surface display, which indicated a direct role of CLIP in the HLA-I antigen presentation pathway. In HLA-I-specific peptide eluates from B-LCLs, five Ii-derived peptides were identified, of which two were from the CLIP region. In vitro peptide binding assays strikingly revealed that the eluted CLIP peptide RMATPLLMQALPM efficiently bound to four distinct HLA-I supertypes (-A2, -B7, -A3, -B40). Furthermore, shorter length variants of this CLIP peptide also bound to these four supertypes, although in silico algorithms only predicted binding to HLA-A2 or -B7. Immunization of HLA-A2 transgenic mice with these peptides did not induce CTL responses. Together these data show a remarkable promiscuity of CLIP for binding to a wide variety of HLA-I molecules. The found participation of CLIP in the HLA-I antigen presentation pathway could reflect an aberrant mechanism in leukemic cells, but might also lead to elucidation of novel processing pathways or immune escape mechanisms.Marvin M van LuijnArjan A van de LoosdrechtMargit H LampenPeter A van VeelenAdri ZevenbergenMichel G D KesterArnoud H de RuGert J OssenkoppeleThorbald van HallS Marieke van HamPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e34649 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marvin M van Luijn Arjan A van de Loosdrecht Margit H Lampen Peter A van Veelen Adri Zevenbergen Michel G D Kester Arnoud H de Ru Gert J Ossenkoppele Thorbald van Hall S Marieke van Ham Promiscuous binding of invariant chain-derived CLIP peptide to distinct HLA-I molecules revealed in leukemic cells.
description	Antigen presentation by HLA class I (HLA-I) and HLA class II (HLA-II) complexes is achieved by proteins that are specific for their respective processing pathway. The invariant chain (Ii)-derived peptide CLIP is required for HLA-II-mediated antigen presentation by stabilizing HLA-II molecules before antigen loading through transient and promiscuous binding to different HLA-II peptide grooves. Here, we demonstrate alternative binding of CLIP to surface HLA-I molecules on leukemic cells. In HLA-II-negative AML cells, we found plasma membrane display of the CLIP peptide. Silencing Ii in AML cells resulted in reduced HLA-I cell surface display, which indicated a direct role of CLIP in the HLA-I antigen presentation pathway. In HLA-I-specific peptide eluates from B-LCLs, five Ii-derived peptides were identified, of which two were from the CLIP region. In vitro peptide binding assays strikingly revealed that the eluted CLIP peptide RMATPLLMQALPM efficiently bound to four distinct HLA-I supertypes (-A2, -B7, -A3, -B40). Furthermore, shorter length variants of this CLIP peptide also bound to these four supertypes, although in silico algorithms only predicted binding to HLA-A2 or -B7. Immunization of HLA-A2 transgenic mice with these peptides did not induce CTL responses. Together these data show a remarkable promiscuity of CLIP for binding to a wide variety of HLA-I molecules. The found participation of CLIP in the HLA-I antigen presentation pathway could reflect an aberrant mechanism in leukemic cells, but might also lead to elucidation of novel processing pathways or immune escape mechanisms.
format	article
author	Marvin M van Luijn Arjan A van de Loosdrecht Margit H Lampen Peter A van Veelen Adri Zevenbergen Michel G D Kester Arnoud H de Ru Gert J Ossenkoppele Thorbald van Hall S Marieke van Ham
author_facet	Marvin M van Luijn Arjan A van de Loosdrecht Margit H Lampen Peter A van Veelen Adri Zevenbergen Michel G D Kester Arnoud H de Ru Gert J Ossenkoppele Thorbald van Hall S Marieke van Ham
author_sort	Marvin M van Luijn
title	Promiscuous binding of invariant chain-derived CLIP peptide to distinct HLA-I molecules revealed in leukemic cells.
title_short	Promiscuous binding of invariant chain-derived CLIP peptide to distinct HLA-I molecules revealed in leukemic cells.
title_full	Promiscuous binding of invariant chain-derived CLIP peptide to distinct HLA-I molecules revealed in leukemic cells.
title_fullStr	Promiscuous binding of invariant chain-derived CLIP peptide to distinct HLA-I molecules revealed in leukemic cells.
title_full_unstemmed	Promiscuous binding of invariant chain-derived CLIP peptide to distinct HLA-I molecules revealed in leukemic cells.
title_sort	promiscuous binding of invariant chain-derived clip peptide to distinct hla-i molecules revealed in leukemic cells.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/c4a5eb86be014846968ef1aa4463edb1
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Promiscuous binding of invariant chain-derived CLIP peptide to distinct HLA-I molecules revealed in leukemic cells.

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