Publication date: Dec 13, 2024
Major histocompatibility complex class II (MHCII) bound to a peptide antigen mediates interactions between CD4 T cells and antigen-presenting cells. Targeting peptide-MHCII with T cell antigen receptors (TCRs) and TCR-like antibodies has shown promise for autoimmune diseases and microbiome tolerance. To develop a general targeting approach, we introduce targeted recognition of antigen-MHC complex reporter for MHCII (TRACeR-II) for the rapid development of peptide-specific MHCII binders. TRACeR-II binders have a small helical bundle scaffold and use a single loop to recognize peptide-MHCII, which offers versatility and enables structural modeling of the interactions to target MHCII antigens. We demonstrate rapid generation of TRACeR-II binders to multiple molecules with affinities in the low-nanomolar to low-micromolar range, comparable to best-in-class TCRs and antibodies. Through computational protein design, we created specific binding sequences in silico from only the sequence of a severe acute respiratory syndrome coronavirus 2 peptide. TRACeR-II provides a straightforward approach to target antigen-MHCII without relying on combinatorial selection on complementarity-determining region loops.
Concepts | Keywords |
---|---|
Antibodies | Antigen |
Biotechnol | Binders |
Cd4 | Class |
Coronavirus | Complex |
Nanomolar | General |
Ii | |
Interactions | |
Loop | |
Mhc | |
Mhcii | |
Peptide | |
Single | |
Targeting | |
Tcrs | |
Tracer |
Semantics
Type | Source | Name |
---|---|---|
disease | MESH | histocompatibility |
disease | IDO | cell |
disease | MESH | autoimmune diseases |
disease | IDO | protein |