Affinity Maturation of a T-Cell Receptor-Like Antibody Specific for a Cytomegalovirus pp65-Derived Peptide Presented by HLA-A*02:01.
Int J Mol Sci
; 22(5)2021 Feb 26.
Article
de En
| MEDLINE
| ID: mdl-33652936
ABSTRACT
Human cytomegalovirus (CMV) infection is widespread among adults (60-90%) and is usually undetected in healthy individuals without symptoms but can cause severe diseases in immunocompromised hosts. T-cell receptor (TCR)-like antibodies (Abs), which recognize complex antigens (peptide-MHC complex, pMHC) composed of MHC molecules with embedded short peptides derived from intracellular proteins, including pathogenic viral proteins, can serve as diagnostic and/or therapeutic agents. In this study, we aimed to engineer a TCR-like Ab specific for pMHC comprising a CMV pp65 protein-derived peptide (495NLVPMVATV503; hereafter, CMVpp65495-503) in complex with MHC-I molecule human leukocyte antigen (HLA)-A*0201 (CMVpp65495-503/HLA-A*0201) to increase affinity by sequential mutagenesis of complementarity-determining regions using yeast surface display technology. Compared with the parental Ab, the final generated Ab (C1-17) showed ~67-fold enhanced binding affinity (KD ≈ 5.2 nM) for the soluble pMHC, thereby detecting the cell surface-displayed CMVpp65495-503/HLA-A*0201 complex with high sensitivity and exquisite specificity. Thus, the new high-affinity TCR-like Ab may be used for the detection and treatment of CMV infection.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Récepteurs aux antigènes des cellules T
/
Antigènes HLA-A
/
Protéines de la matrice virale
/
Infections à cytomégalovirus
/
Cytomegalovirus
/
Anticorps
Limites:
Humans
Langue:
En
Journal:
Int J Mol Sci
Année:
2021
Type de document:
Article