PMID- 32117208
OWN - NLM
STAT- MEDLINE
DCOM- 20201118
LR  - 20240329
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 10
DP  - 2019
TI  - Major Histocompatibility Complex Binding, Eluted Ligands, and Immunogenicity: 
      Benchmark Testing and Predictions.
PG  - 3151
LID - 10.3389/fimmu.2019.03151 [doi]
LID - 3151
AB  - Antidrug antibody (ADA) responses impact drug safety, potency, and efficacy. It 
      is generally assumed that ADA responses are associated with human leukocyte 
      antigen (HLA) class II-restricted CD4+ T-cell reactivity. Although this review 
      does not address ADA responses per se, the analysis presented here is relevant to 
      the topic, because measuring or predicting CD4+ T-cell reactivity is a common 
      strategy to address ADA and immunogenicity concerns. Because human CD4+ T-cell 
      reactivity relies on the recognition of peptides bound to HLA class II, 
      prediction, or measurement of the capacity of different peptides to bind or be 
      natural ligands of HLA class II is used as a predictor of CD4+ T-cell reactivity 
      and ADA development. Thus, three different interconnected variables are commonly 
      utilized in predicting T-cell reactivity: major histocompatibility complex (MHC) 
      binding, capacity to be generated as natural HLA ligands, and T-cell 
      immunogenicity. To provide the scientific community with guidance in the relative 
      merit of different approaches, it is necessary to clearly define what outcomes 
      are being considered. Thus, the accuracy of HLA binding predictions varies as a 
      function of what the outcome predicted is, whether it is binding itself, natural 
      processing, or T-cell immunogenicity. Furthermore, it is necessary that the 
      accuracy of prediction is based on rigorous benchmarking, grounded by fair, 
      objective, transparent, and experimental criteria. In this review, we provide our 
      perspective on how different variables and methodologies predict each of the 
      various outcomes and point out knowledge gaps and areas to be addressed by 
      further experimental work.
CI  - Copyright (c) 2020 Paul, Grifoni, Peters and Sette.
FAU - Paul, Sinu
AU  - Paul S
AD  - Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA, 
      United States.
FAU - Grifoni, Alba
AU  - Grifoni A
AD  - Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA, 
      United States.
FAU - Peters, Bjoern
AU  - Peters B
AD  - Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA, 
      United States.
AD  - Department of Medicine, University of California, San Diego, San Diego, CA, 
      United States.
FAU - Sette, Alessandro
AU  - Sette A
AD  - Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA, 
      United States.
AD  - Department of Medicine, University of California, San Diego, San Diego, CA, 
      United States.
LA  - eng
GR  - 75N93019C00001/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
DEP - 20200205
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Ligands)
SB  - IM
MH  - Animals
MH  - Benchmarking
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - Epitopes, T-Lymphocyte/immunology
MH  - Histocompatibility Antigens Class II/*immunology
MH  - Humans
MH  - Immunologic Techniques/*standards
MH  - Ligands
MH  - Protein Binding/immunology
PMC - PMC7012937
OTO - NOTNLM
OT  - CD4 T cell
OT  - MHC-prediction
OT  - anti drug antibodies (ADA)
OT  - immunogenicity
OT  - prediction benchmarking
EDAT- 2020/03/03 06:00
MHDA- 2020/11/20 06:00
PMCR- 2019/01/01
CRDT- 2020/03/03 06:00
PHST- 2019/10/29 00:00 [received]
PHST- 2019/12/30 00:00 [accepted]
PHST- 2020/03/03 06:00 [entrez]
PHST- 2020/03/03 06:00 [pubmed]
PHST- 2020/11/20 06:00 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2019.03151 [doi]
PST - epublish
SO  - Front Immunol. 2020 Feb 5;10:3151. doi: 10.3389/fimmu.2019.03151. eCollection 
      2019.