PMID- 36909546
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231016
DP  - 2023 Feb 27
TI  - Mass spectrometric profiling of HLA-B44 peptidomes provides evidence for 
      tapasin-mediated tryptophan editing.
LID - 2023.02.26.530125 [pii]
LID - 10.1101/2023.02.26.530125 [doi]
AB  - 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 tapasinindependent. 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.
FAU - Kaur, Amanpreet
AU  - Kaur A
AD  - Department of Microbiology and Immunology, University of Michigan Medical School, 
      Ann Arbor, MI, USA.
FAU - Surnilla, Avrokin
AU  - Surnilla A
AD  - Department of Microbiology and Immunology, University of Michigan Medical School, 
      Ann Arbor, MI, USA.
FAU - Zaitouna, Anita J
AU  - Zaitouna AJ
AD  - Department of Microbiology and Immunology, University of Michigan Medical School, 
      Ann Arbor, MI, USA.
FAU - Basrur, Venkatesha
AU  - Basrur V
AD  - Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, 
      USA.
FAU - Mumphrey, Michael B
AU  - Mumphrey MB
AD  - Department of Computational Medicine and Bioinformatics, University of Michigan 
      Medical School, Ann Arbor, MI, USA.
FAU - Grigorova, Irina
AU  - Grigorova I
AD  - Department of Microbiology and Immunology, University of Michigan Medical School, 
      Ann Arbor, MI, USA.
FAU - Cieslik, Marcin
AU  - Cieslik M
AD  - Department of Computational Medicine and Bioinformatics, University of Michigan 
      Medical School, Ann Arbor, MI, USA.
FAU - Carrington, Mary
AU  - Carrington M
AD  - Basic Science Program, Frederick National Laboratory for Cancer Research, 
      National Cancer Institute, Frederick, MD, USA.
AD  - Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National 
      Cancer Institute, Bethesda, MD, USA.
AD  - Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
FAU - Nesvizhskii, Alexey I
AU  - Nesvizhskii AI
AD  - Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, 
      USA.
AD  - Department of Computational Medicine and Bioinformatics, University of Michigan 
      Medical School, Ann Arbor, MI, USA.
FAU - Raghavan, Malini
AU  - Raghavan M
AD  - Department of Microbiology and Immunology, University of Michigan Medical School, 
      Ann Arbor, MI, USA.
LA  - eng
GR  - U24 CA271037/CA/NCI NIH HHS/United States
GR  - R01 GM094231/GM/NIGMS NIH HHS/United States
GR  - P50 CA186786/CA/NCI NIH HHS/United States
GR  - R21 AI164025/AI/NIAID NIH HHS/United States
GR  - HHSN261200800001C/RC/CCR NIH HHS/United States
GR  - T32 AI007413/AI/NIAID NIH HHS/United States
GR  - HHSN261200800001E/CA/NCI NIH HHS/United States
GR  - T32 AI007528/AI/NIAID NIH HHS/United States
GR  - R01 AI044115/AI/NIAID NIH HHS/United States
PT  - Preprint
DEP - 20230227
PL  - United States
TA  - bioRxiv
JT  - bioRxiv : the preprint server for biology
JID - 101680187
UIN - J Immunol. 2023 Sep 22;:. PMID: 37737643
PMC - PMC10002704
COIS- Conflicts of Interest All the authors have no conflicts of interest to declare.
EDAT- 2023/03/14 06:00
MHDA- 2023/03/14 06:01
PMCR- 2023/03/10
CRDT- 2023/03/13 04:00
PHST- 2023/03/13 04:00 [entrez]
PHST- 2023/03/14 06:00 [pubmed]
PHST- 2023/03/14 06:01 [medline]
PHST- 2023/03/10 00:00 [pmc-release]
AID - 2023.02.26.530125 [pii]
AID - 10.1101/2023.02.26.530125 [doi]
PST - epublish
SO  - bioRxiv [Preprint]. 2023 Feb 27:2023.02.26.530125. doi: 
      10.1101/2023.02.26.530125.