Conformation-Specific HLA-F Antibodies Enable Next-Generation Immune Profiling

SUMMARY

A panel of antibody-based reagents has been developed to distinguish two conformational states of the nonclassical MHC protein HLA-F: an open conformer form and a peptide-loaded form.

The Unmet Need: Researchers currently lack reliable reagents that can distinguish biologically distinct conformational states of HLA-F on cells and tissues

• Current antibodies, including widely used commercial ones, lack the capability to discriminate between the open conformer and peptide-loaded states of HLA-F, which limits understanding of HLA-F’s distinct roles in cancer, viral infections, and autoimmune disorders such as ALS. This impedes detailed study of HLA-F’s expression and function in various pathological and physiological conditions.

• The emergence of targeted immunotherapies and precision diagnostics fosters demand for molecular reagents that can selectively recognize protein conformations, enabling refined immune profiling and improved intervention strategies. Advanced antibody engineering and biophysical characterization methods create an opportunity for the development of such highly specific reagents.

The Proposed Solution: Highly specific antibodies differentiating between peptide-free and peptide-loaded HLA-F conformers using Fab fragment engineering

• The faculty inventor developed novel antibodies, engineered as Fab fragments with defined sequences, that selectively bind either the open conformer (ocHLA-F) or the peptide-loaded form (pHLA-F) of HLA-F, a distinguishing feature not achieved by current commercial antibodies like which show cross-reactivity.

• Validation through phage display selection and surface plasmon resonance confirms their high specificity and affinity, with staining experiments on multiple cell lines demonstrating their ability to differentiate between HLA-F conformations in situ, thus enabling detailed studies of expression patterns relevant to disease mechanisms. These reagents represent a foundation for further development into full IgG antibodies for broader diagnostic and therapeutic applications.

ADVANTAGES

• High specificity for distinct HLA-F conformations

• Reduced cross-reactivity with related proteins

• Validated by phage display and SPR binding assays

• Capability for cell-based staining and phenotyping

APPLICATIONS

• Immunophenotyping in cancer and viral infections

• Diagnostic differentiation in autoimmune diseases including ALS

• Development of targeted immunotherapies and biomarker assays