PMID- 37759665
OWN - NLM
STAT- Publisher
LR  - 20231003
IS  - 2079-7737 (Print)
IS  - 2079-7737 (Electronic)
IS  - 2079-7737 (Linking)
VI  - 12
IP  - 9
DP  - 2023 Sep 21
TI  - Expanding the MAPPs Assay to Accommodate MHC-II Pan Receptors for Improved 
      Predictability of Potential T Cell Epitopes.
LID - 10.3390/biology12091265 [doi]
LID - 1265
AB  - A critical step in the immunogenicity cascade is attributed to human leukocyte 
      antigen (HLA) II presentation triggering T cell immune responses. The liquid 
      chromatography-tandem mass spectrometry (LC-MS/MS)-based major histocompatibility 
      complex (MHC) II-associated peptide proteomics (MAPPs) assay is implemented 
      during preclinical risk assessments to identify biotherapeutic-derived T cell 
      epitopes. Although studies indicate that HLA-DP and HLA-DQ alleles are linked to 
      immunogenicity, most MAPPs studies are restricted to using HLA-DR as the dominant 
      HLA II genotype due to the lack of well-characterized immunoprecipitating 
      antibodies. Here, we address this issue by testing various commercially available 
      clones of MHC-II pan (CR3/43, WR18, and Tu39), HLA-DP (B7/21), and HLA-DQ (SPV-L3 
      and 1a3) antibodies in the MAPPs assay, and characterizing identified peptides 
      according to binding specificity. Our results reveal that HLA II 
      receptor-precipitating reagents with similar reported specificities differ based 
      on clonality and that MHC-II pan antibodies do not entirely exhibit pan-specific 
      tendencies. Since no individual antibody clone is able to recover the complete 
      HLA II peptide repertoire, we recommend a mixed strategy of clones L243, WR18, 
      and SPV-L3 in a single immunoprecipitation step for more robust compound-specific 
      peptide detection. Ultimately, our optimized MAPPs strategy improves the 
      predictability and additional identification of T cell epitopes in immunogenicity 
      risk assessments.
FAU - Hartman, Katharina
AU  - Hartman K
AUID- ORCID: 0009-0006-0509-516X
AD  - Roche Pharma Research and Early Development, Roche Innovation Center Basel, 
      Grenzacherstrasse 124, 4070 Basel, Switzerland.
FAU - Steiner, Guido
AU  - Steiner G
AUID- ORCID: 0000-0002-0062-4089
AD  - Roche Pharma Research and Early Development, Roche Innovation Center Basel, 
      Grenzacherstrasse 124, 4070 Basel, Switzerland.
FAU - Siegel, Michel
AU  - Siegel M
AUID- ORCID: 0009-0003-2858-4247
AD  - Roche Pharma Research and Early Development, Roche Innovation Center Basel, 
      Grenzacherstrasse 124, 4070 Basel, Switzerland.
FAU - Looney, Cary M
AU  - Looney CM
AD  - Roche Pharma Research and Early Development, Roche Innovation Center Basel, 
      Grenzacherstrasse 124, 4070 Basel, Switzerland.
FAU - Hickling, Timothy P
AU  - Hickling TP
AUID- ORCID: 0000-0002-8918-2140
AD  - Roche Pharma Research and Early Development, Roche Innovation Center Basel, 
      Grenzacherstrasse 124, 4070 Basel, Switzerland.
FAU - Bray-French, Katharine
AU  - Bray-French K
AUID- ORCID: 0000-0003-4184-1546
AD  - Roche Pharma Research and Early Development, Roche Innovation Center Basel, 
      Grenzacherstrasse 124, 4070 Basel, Switzerland.
FAU - Springer, Sebastian
AU  - Springer S
AUID- ORCID: 0000-0002-5527-6149
AD  - School of Science, Department of Biochemistry and Cell Biology, Constructor 
      University, Campus Ring 1, 28759 Bremen, Germany.
FAU - Marban-Doran, Celine
AU  - Marban-Doran C
AD  - Roche Pharma Research and Early Development, Roche Innovation Center Basel, 
      Grenzacherstrasse 124, 4070 Basel, Switzerland.
FAU - Ducret, Axel
AU  - Ducret A
AUID- ORCID: 0000-0003-1251-8520
AD  - Roche Pharma Research and Early Development, Roche Innovation Center Basel, 
      Grenzacherstrasse 124, 4070 Basel, Switzerland.
LA  - eng
PT  - Journal Article
DEP - 20230921
PL  - Switzerland
TA  - Biology (Basel)
JT  - Biology
JID - 101587988
PMC - PMC10525474
OTO - NOTNLM
OT  - HLA II receptors
OT  - MAPPs assay
OT  - NetMHCIIpan
OT  - T cell epitope
OT  - anti-drug antibody
OT  - immunogenicity
OT  - immunopeptidomics
OT  - in silico analysis
OT  - mass spectrometry
OT  - therapeutic antibodies
COIS- K. Hartman, G. Steiner, M. Siegel, C.M. Looney, T.P. Hickling, K. Bray-French, C. 
      Marban-Doran and A. Ducret are employees of the Roche Group.
EDAT- 2023/09/28 06:42
MHDA- 2023/09/28 06:42
PMCR- 2023/09/21
CRDT- 2023/09/28 01:02
PHST- 2023/08/27 00:00 [received]
PHST- 2023/09/08 00:00 [revised]
PHST- 2023/09/11 00:00 [accepted]
PHST- 2023/09/28 06:42 [medline]
PHST- 2023/09/28 06:42 [pubmed]
PHST- 2023/09/28 01:02 [entrez]
PHST- 2023/09/21 00:00 [pmc-release]
AID - biology12091265 [pii]
AID - biology-12-01265 [pii]
AID - 10.3390/biology12091265 [doi]
PST - epublish
SO  - Biology (Basel). 2023 Sep 21;12(9):1265. doi: 10.3390/biology12091265.