Cargando…
Mass spectrometric profiling of HLA-B44 peptidomes provides evidence for tapasin-mediated tryptophan editing
Activation of CD8(+) T cells against pathogens and cancers involves the recognition of antigenic peptides bound to human leukocyte antigen (HLA) class-I proteins. Peptide binding to HLA class I proteins is coordinated by a multi-protein complex called the peptide loading complex (PLC). Tapasin, a ke...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10002704/ https://www.ncbi.nlm.nih.gov/pubmed/36909546 http://dx.doi.org/10.1101/2023.02.26.530125 |
_version_ | 1784904445288513536 |
---|---|
author | Kaur, Amanpreet Surnilla, Avrokin Zaitouna, Anita J. Basrur, Venkatesha Mumphrey, Michael B. Grigorova, Irina Cieslik, Marcin Carrington, Mary Nesvizhskii, Alexey I. Raghavan, Malini |
author_facet | Kaur, Amanpreet Surnilla, Avrokin Zaitouna, Anita J. Basrur, Venkatesha Mumphrey, Michael B. Grigorova, Irina Cieslik, Marcin Carrington, Mary Nesvizhskii, Alexey I. Raghavan, Malini |
author_sort | Kaur, Amanpreet |
collection | PubMed |
description | Activation of CD8(+) T cells against pathogens and cancers involves the recognition of antigenic peptides bound to human leukocyte antigen (HLA) class-I proteins. Peptide binding to HLA class I proteins is coordinated by a multi-protein complex called the peptide loading complex (PLC). Tapasin, a key PLC component, facilitates the binding and optimization of HLA class I peptides. However, different HLA class I allotypes have variable requirements for tapasin for their assembly and surface expression. HLA-B*44:02 and HLA-B*44:05, which differ only at residue 116 of their heavy chain sequences, fall at opposite ends of the tapasin-dependency spectrum. HLA-B*44:02 (D116) is highly tapasin-dependent, whereas HLA-B*44:05 (Y116) is highly tapasin-independent. Mass spectrometric comparisons of HLA-B*4405 and HLA-B*44:02 peptidomes were undertaken to better understand the influences of tapasin upon HLA-B44 peptidome compositions. Analyses of the HLA-B*44:05 peptidomes in the presence and absence of tapasin reveal that peptides with the C-terminal tryptophan residues and those with higher predicted binding affinities are selected in the presence of tapasin. Additionally, when tapasin is present, C-terminal tryptophans are also more highly represented among peptides unique to B*44:02 and those shared between B*44:02 and B*44:05, compared with peptides unique to B*44:05. Overall, our findings demonstrate that tapasin influences the C-terminal composition of HLA class I-bound peptides and favors the binding of higher affinity peptides. For the HLA-B44 family, the presence of tapasin or high tapasin-dependence of an allotype results in better binding of peptides with C-terminal tryptophans, consistent with a role for tapasin in stabilizing an open conformation to accommodate bulky C-terminal residues. |
format | Online Article Text |
id | pubmed-10002704 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-100027042023-03-11 Mass spectrometric profiling of HLA-B44 peptidomes provides evidence for tapasin-mediated tryptophan editing Kaur, Amanpreet Surnilla, Avrokin Zaitouna, Anita J. Basrur, Venkatesha Mumphrey, Michael B. Grigorova, Irina Cieslik, Marcin Carrington, Mary Nesvizhskii, Alexey I. Raghavan, Malini bioRxiv Article Activation of CD8(+) T cells against pathogens and cancers involves the recognition of antigenic peptides bound to human leukocyte antigen (HLA) class-I proteins. Peptide binding to HLA class I proteins is coordinated by a multi-protein complex called the peptide loading complex (PLC). Tapasin, a key PLC component, facilitates the binding and optimization of HLA class I peptides. However, different HLA class I allotypes have variable requirements for tapasin for their assembly and surface expression. HLA-B*44:02 and HLA-B*44:05, which differ only at residue 116 of their heavy chain sequences, fall at opposite ends of the tapasin-dependency spectrum. HLA-B*44:02 (D116) is highly tapasin-dependent, whereas HLA-B*44:05 (Y116) is highly tapasin-independent. Mass spectrometric comparisons of HLA-B*4405 and HLA-B*44:02 peptidomes were undertaken to better understand the influences of tapasin upon HLA-B44 peptidome compositions. Analyses of the HLA-B*44:05 peptidomes in the presence and absence of tapasin reveal that peptides with the C-terminal tryptophan residues and those with higher predicted binding affinities are selected in the presence of tapasin. Additionally, when tapasin is present, C-terminal tryptophans are also more highly represented among peptides unique to B*44:02 and those shared between B*44:02 and B*44:05, compared with peptides unique to B*44:05. Overall, our findings demonstrate that tapasin influences the C-terminal composition of HLA class I-bound peptides and favors the binding of higher affinity peptides. For the HLA-B44 family, the presence of tapasin or high tapasin-dependence of an allotype results in better binding of peptides with C-terminal tryptophans, consistent with a role for tapasin in stabilizing an open conformation to accommodate bulky C-terminal residues. Cold Spring Harbor Laboratory 2023-02-27 /pmc/articles/PMC10002704/ /pubmed/36909546 http://dx.doi.org/10.1101/2023.02.26.530125 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator. |
spellingShingle | Article Kaur, Amanpreet Surnilla, Avrokin Zaitouna, Anita J. Basrur, Venkatesha Mumphrey, Michael B. Grigorova, Irina Cieslik, Marcin Carrington, Mary Nesvizhskii, Alexey I. Raghavan, Malini Mass spectrometric profiling of HLA-B44 peptidomes provides evidence for tapasin-mediated tryptophan editing |
title | Mass spectrometric profiling of HLA-B44 peptidomes provides evidence for tapasin-mediated tryptophan editing |
title_full | Mass spectrometric profiling of HLA-B44 peptidomes provides evidence for tapasin-mediated tryptophan editing |
title_fullStr | Mass spectrometric profiling of HLA-B44 peptidomes provides evidence for tapasin-mediated tryptophan editing |
title_full_unstemmed | Mass spectrometric profiling of HLA-B44 peptidomes provides evidence for tapasin-mediated tryptophan editing |
title_short | Mass spectrometric profiling of HLA-B44 peptidomes provides evidence for tapasin-mediated tryptophan editing |
title_sort | mass spectrometric profiling of hla-b44 peptidomes provides evidence for tapasin-mediated tryptophan editing |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10002704/ https://www.ncbi.nlm.nih.gov/pubmed/36909546 http://dx.doi.org/10.1101/2023.02.26.530125 |
work_keys_str_mv | AT kauramanpreet massspectrometricprofilingofhlab44peptidomesprovidesevidencefortapasinmediatedtryptophanediting AT surnillaavrokin massspectrometricprofilingofhlab44peptidomesprovidesevidencefortapasinmediatedtryptophanediting AT zaitounaanitaj massspectrometricprofilingofhlab44peptidomesprovidesevidencefortapasinmediatedtryptophanediting AT basrurvenkatesha massspectrometricprofilingofhlab44peptidomesprovidesevidencefortapasinmediatedtryptophanediting AT mumphreymichaelb massspectrometricprofilingofhlab44peptidomesprovidesevidencefortapasinmediatedtryptophanediting AT grigorovairina massspectrometricprofilingofhlab44peptidomesprovidesevidencefortapasinmediatedtryptophanediting AT cieslikmarcin massspectrometricprofilingofhlab44peptidomesprovidesevidencefortapasinmediatedtryptophanediting AT carringtonmary massspectrometricprofilingofhlab44peptidomesprovidesevidencefortapasinmediatedtryptophanediting AT nesvizhskiialexeyi massspectrometricprofilingofhlab44peptidomesprovidesevidencefortapasinmediatedtryptophanediting AT raghavanmalini massspectrometricprofilingofhlab44peptidomesprovidesevidencefortapasinmediatedtryptophanediting |