PMID- 36605211
OWN - NLM
STAT- MEDLINE
DCOM- 20230109
LR  - 20230815
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 13
DP  - 2022
TI  - The HLA class-II immunopeptidomes of AAV capsids proteins.
PG  - 1067399
LID - 10.3389/fimmu.2022.1067399 [doi]
LID - 1067399
AB  - INTRODUCTION: Gene therapies are using Adeno-associated viruses (AAVs) as 
      vectors, but immune responses against the capsids pose challenges to their 
      efficiency and safety. Helper T cell recognition of capsid-derived peptides bound 
      to human leukocyte antigen (HLA) class II molecules is an essential step in the 
      AAV-specific adaptive immunity. METHODS: Using MHC-associated peptide proteomics, 
      we identified the HLA-DR and HLA-DQ immunopeptidomes of the capsid proteins of 
      three different AAV serotypes (AAV2, AAV6, and AAV9) from a panel of healthy 
      donors selected to represent a majority of allele usage. RESULTS: The identified 
      sequences span the capsids of all serotypes, with AAV2 having the highest peptide 
      count. For all the serotypes, multiple promiscuous peptides were identified and 
      displayed by both HLA-DR and -DQ. However, despite high sequence homology, there 
      were few identical peptides among AAV2, AAV6, and AAV9 immunopeptidomes, and none 
      were promiscuous. DISCUSSION: Results from this work represent a comprehensive 
      immunopeptidomics research of potential CD4+ T cell epitopes and provide the 
      basis for immunosurveillance efforts for safer and more efficient AAV-based gene 
      therapies.
CI  - Copyright (c) 2022 Brito-Sierra, Lannan, Siegel and Malherbe.
FAU - Brito-Sierra, Carlos A
AU  - Brito-Sierra CA
AD  - Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, United 
      States.
FAU - Lannan, Megan B
AU  - Lannan MB
AD  - Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, United 
      States.
FAU - Siegel, Robert W
AU  - Siegel RW
AD  - Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, United 
      States.
FAU - Malherbe, Laurent P
AU  - Malherbe LP
AD  - Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, United 
      States.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221220
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Capsid Proteins)
RN  - 0 (Peptides)
RN  - 0 (HLA Antigens)
SB  - IM
EIN - Front Immunol. 2023 Jul 27;14:1261322. PMID: 37575262
MH  - Humans
MH  - *Capsid Proteins/genetics
MH  - *Capsid
MH  - Dependovirus
MH  - Peptides/metabolism
MH  - HLA Antigens/metabolism
PMC - PMC9807805
OTO - NOTNLM
OT  - AAV (Adeno-associated virus)
OT  - CD4+
OT  - HLA
OT  - gene therapy
OT  - immunogenicity
OT  - immunopeptidome
OT  - risk assessment
COIS- All authors are employees and stockholders of Eli Lilly and Company.
EDAT- 2023/01/07 06:00
MHDA- 2023/01/10 06:00
PMCR- 2022/01/01
CRDT- 2023/01/06 02:28
PHST- 2022/10/11 00:00 [received]
PHST- 2022/11/30 00:00 [accepted]
PHST- 2023/01/06 02:28 [entrez]
PHST- 2023/01/07 06:00 [pubmed]
PHST- 2023/01/10 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2022.1067399 [doi]
PST - epublish
SO  - Front Immunol. 2022 Dec 20;13:1067399. doi: 10.3389/fimmu.2022.1067399. 
      eCollection 2022.