HBV Core169 Peptides for HLA-A*11:01 CD8+ T-Cell Detection
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Solution Overview
Problem
Current methods for identifying and manipulating HLA-A*11:01-restricted HBV-specific CD8+ T cells are limited, particularly in Asian populations, where this allele is prevalent, and there is a lack of understanding of their immunogenicity and functional capacity in chronic HBV infection, which affects treatment efficacy.
Innovation Solution
Identification of specific peptides derived from HBVcore169 that bind to HLA-A*1101 and T cell receptors (TCRs) to induce anti-viral T cell responses, including peptides like STLPETAVVRR (SEQ ID No. 21) and TCR sequences such as CASGDSNSPLHF (SEQ ID No. 17), which can be used in immunotherapy to target HBV-infected hepatocytes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If HLA-A*02:01-restricted epitopes are used for identifying HBV-specific CD8+ T cells, then the immunogenicity is well-defined and treatment efficacy is established, but this approach is not applicable to Asian populations where HLA-A*11:01 is the predominant allele
Solution Approach 1:
The patent changes the HLA allele parameter from A*02:01 to A*11:01 to match the predominant allele in Asian populations. This parameter change enables the identification of HBV-specific CD8+ T cells in the correct population context, resolving the contradiction between adaptability to Asian populations and reliability of immunogenicity definition.
2Measurement precision
If virus-specific T cell response is focused on HLA-A*02:01-restricted epitopes, then immunogenicity is well-defined, but the low frequency of HBV-specific T cells remains undetected in other HLA alleles
Solution Approach 1:
The patent changes the HLA restriction parameter to A*11:01, which enables detection of HBV-specific T cells in Asian populations. This parameter change increases measurement precision for detecting low-frequency T cells that would otherwise remain undetected with A*02:01-restricted epitopes.
3Ease of manufacture
If conventional T cell identification methods are used, then the process is simple, but the functional capacity and phenotypic profiles of HBV-specific T cells remain unknown
Solution Approach 1:
The patent performs preliminary characterization of HBV-specific T cells by defining their phenotypic profiles and functional capacities before applying them to treatment. This preliminary action preserves critical information about T cell function and phenotype that would otherwise be lost, while maintaining ease of identification through HLA-A*11:01-restricted epitope targeting.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
These peptides and TCRs enable the selective expansion and targeting of HBV-specific T cells, enhancing immune response and viral control in patients, providing a therapeutic approach for HBV infection.
Implementation Method 1
HLA-A*11:01-restricted hepatitis B virus (HBV) peptides for identifying HBV-specific CD8+ T cells
Implementation Method 2
TCR sequences such as CASGDSNSPLHF (SEQ ID No. 17), which can be used in immunotherapy to target HBV-infected hepatocytes
Data Source
AI summary
The present invention relates to peptides and their ability to identify and bind to T cells specific for HBV-infected hepatocytes. In a first aspect of the invention, there is provided a peptide comprising an amino acid sequence selected from the group consisting of STLPETAVVRR (SEQ ID NO: 21), STLPETAVVR (SEQ ID NO: 22), STLPETTVVRR (SEQ ID NO: 23), STLPETTVTRR (SEQ ID NO: 24), STPPETTVVRR (SEQ ID NO: 25), STLPETTVVGR (SEQ ID NO: 26) and STIPETTVVRR (SEQ ID NO: 27), wherein the peptide is derived from Hepatitis B virus core169 and is capable of binding HLA-A*1101 and when bound to HLA-A*1101 is capable of identifying T cells specific for Hepatitis B virus. In a second aspect of the invention, there is provided a T cell expressing a T cell receptor (TCR) molecule, wherein the TCR molecule comprises an amino acid sequence selected from the group consisting of CASGDSNSPLHF (SEQ ID NO: 17), CASSGGQIVYEQYF (SEQ ID NO: 18), CSARGGRGGDYTF (SEQ ID NO: 19) and CASSQDWTEAFF (SEQ ID NO: 20), and wherein the TCR molecule is able to bind to a peptide according to the first aspect of the invention.