PMID- 35042811
OWN - NLM
STAT- MEDLINE
DCOM- 20220228
LR  - 20220719
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 119
IP  - 4
DP  - 2022 Jan 25
TI  - V-CARMA: A tool for the detection and modification of antigen-specific T cells.
LID - 10.1073/pnas.2116277119 [doi]
LID - e2116277119
AB  - T cells promote our body's ability to battle cancers and infectious diseases but 
      can act pathologically in autoimmunity. The recognition of peptides presented by 
      major histocompatibility complex (pMHC) molecules by T cell receptors (TCRs) 
      enables T cell-mediated responses. To modify disease-relevant T cells, new tools 
      to genetically modify T cells and decode their antigen recognition are needed. 
      Here, we present an approach using viruses pseudotyped with peptides loaded on 
      MHC called V-CARMA (Viral ChimAeric Receptor MHC-Antigen) to specifically target 
      T cells expressing cognate TCRs for antigen discovery and T cell engineering. We 
      show that lentiviruses displaying antigens on human leukocyte antigen (HLA) class 
      I and class II molecules can robustly infect CD8(+) and CD4(+) T cells expressing 
      cognate TCRs, respectively. The infection rates of the pseudotyped lentiviruses 
      (PLVs) are correlated with the binding affinity of the TCR to its cognate 
      antigen. Furthermore, peptide-HLA pseudotyped lentivirus V-CARMA constructs can 
      identify target cells from a mixed T cell population, suppress PD-1 expression on 
      CD8(+) T cells via PDCD1 shRNA delivery, and induce apoptosis in autoreactive 
      CD4(+) T cells. Thus, V-CARMA is a versatile tool for TCR ligand identification 
      and selective T cell manipulation.
CI  - Copyright (c) 2022 the Author(s). Published by PNAS.
FAU - Guo, Xi-Zhi J
AU  - Guo XJ
AD  - Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115.
AD  - Department of Genetics, Harvard Medical School, Boston, MA 02115.
AD  - HHMI, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
FAU - Elledge, Stephen J
AU  - Elledge SJ
AUID- ORCID: 0000-0001-7923-6283
AD  - Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115; 
      selledge@genetics.med.harvard.edu.
AD  - Department of Genetics, Harvard Medical School, Boston, MA 02115.
LA  - eng
GR  - HHMI/Howard Hughes Medical Institute/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Lymphokines)
RN  - 0 (Peptides)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Receptors, Antigen, T-Cell, alpha-beta)
RN  - 0 (Receptors, Chimeric Antigen)
RN  - 0 (antigen-specific helper factors)
SB  - IM
MH  - Antigens/immunology
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Genetic Engineering/*methods
MH  - Histocompatibility Antigens Class I/immunology
MH  - Humans
MH  - Immunotherapy/*methods
MH  - Lentivirus/genetics/immunology
MH  - Lymphocyte Activation
MH  - Lymphokines/*metabolism/physiology
MH  - Major Histocompatibility Complex
MH  - Peptides/metabolism
MH  - Receptors, Antigen, T-Cell/genetics/immunology
MH  - Receptors, Antigen, T-Cell, alpha-beta/genetics
MH  - Receptors, Chimeric Antigen/genetics
PMC - PMC8795542
OTO - NOTNLM
OT  - T cell modification
OT  - peptide-MHC complex
OT  - pseudotyped lentivirus
COIS- Competing interest statement: S.J.E. is a founder of TScan Therapeutics, Maze 
      Therapeutics, ImmuneID and Mirimus; a scientific advisory board member for 
      Homology Medicines, TScan Therapeutics, Maze Therapeutics, and ImmuneID; and an 
      advisor for MPM Capital.
EDAT- 2022/01/20 06:00
MHDA- 2022/03/01 06:00
PMCR- 2022/07/18
CRDT- 2022/01/19 06:43
PHST- 2021/12/13 00:00 [accepted]
PHST- 2022/01/19 06:43 [entrez]
PHST- 2022/01/20 06:00 [pubmed]
PHST- 2022/03/01 06:00 [medline]
PHST- 2022/07/18 00:00 [pmc-release]
AID - 2116277119 [pii]
AID - 202116277 [pii]
AID - 10.1073/pnas.2116277119 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2022 Jan 25;119(4):e2116277119. doi: 
      10.1073/pnas.2116277119.