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A TCR blocking HLA-A*11:01-specific human monoclonal antibody

ABSTRACT: Cross-linking mass spectrometry and Targeted cross-linking mass spectrometry for a TCR blocking human monoclonal antibody targeting HLA-A*11:01

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Nicholas R.J. Gascoigne

PROVIDER: PXD053836 | JPOST Repository | Mon Jun 02 00:00:00 GMT+01:00 2025

REPOSITORIES: jPOST

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Dataset's files

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			Action	DRS
	1H5A11_PRM_skylinefiles.zip	Other
	1H5_A11_sequences.fasta	Fasta
	2021-07-28-08-35-55_1H5_DSSO_NF_R123.zip	Other
	2021-07-28-22-18-55_1H5_SDA_NF_R123.zip	Other
	20210728_ZS_1H5A11_DSSO_NF_R1.raw	Raw

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1 - 5 of 18

Publications

Occlusion of TCR binding to HLA-A*11:01 by a non-pathogenic human alloantibody.

Hamidinia Maryam M Gu Yue Y Ser Zheng Z Brzostek Joanna J Tay Neil Q NQ Yap Jiawei J Chua Yen Leong YL Lim Yan Ting YT Wood Kathryn J KJ Vathsala Anantharaman A Sobota Radoslaw M RM MacAry Paul A PA Gascoigne Nicholas R J NRJ

Cellular and molecular life sciences : CMLS 20250226 1

Over the last decades, organ transplantation has made rapid progress as a curative therapy for organ failure. However, the adaptive immune system-alloreactive T cells and antibodies targeting human leukocyte antigens (HLA)-is the leading cause of graft rejection. The presence of anti-donor HLA antibodies is considered a risk factor that disqualifies a particular donor-recipient pair. However, alloantibodies are found in some long-term graft survivors, suggesting a protective blocking function of ...[more]

PMID: 40009199

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Project description:Few non-classical HLA-E restricted HIV-specific epitopes have been described, and even less is known about the functional profile of responding CD8 T cells (CD8s). This study evaluates the functional characteristics of CD8s targeting the Gag epitope (KAFSPEVIPMF or KF11) based on their restriction by either HLA-E (E-CD8s) or HLA-B57 (B57-CD8s). CD8s from 8 people with HIV (PWH) were cocultured with KF11 peptide presented by cell lines expressing HLA-B*57:01, HLA-E*01:01 or E*01:03. CD8s were analyzed through single-cell (sc) RNA and TCR sequencing. Additionally, supernatants were analyzed for soluble proteomics using a Luminex assay. B57-CD8s secreted higher levels of cytotoxic cytokines such as IFNγ, while E-CD8s produced more chemotactic cytokines, including RANTES, CXCL10 (IP-10), and IL27confirmed through scRNAseq. Despite distinct cytokine profiles, TCR clonotypes stimulated by KF11 were cross-restricted by HLA-B*57 and HLA-E*01/03. In vitro T cell reporter assays clearly demonstrated this cross-restriction. A TRAV5-containing metaclonotype cluster was seen in PWH with lower viral loads. These findings demonstrate that HIV-specific CD8s in PWH exhibit cross HLA-B*57 and HLA-E*01/03 restriction, resulting in functionally distinct immune responses that may contribute to HIV control.

2025-12-11 | GSE306023 | GEO

CD8 T cells cross-restricted by HLA-B*57 and HLA-E*01 recognize HIV Gag with different functional profiles [dataset 1]

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2023-11-23 | PXD038059 | JPOST Repository

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Project description:T-cell based therapies have shown remarkable efficacy in multiple myeloma (MM), yet the disease remains largely incurable. Here, we investigated the constant domains of the immunoglobulin heavy chain (IgH) as novel targets for therapeutic T-cell receptors (TCRs), after confirming high and homogeneous IGH expression in >95% of MM patients. MM cells secrete excessive monoclonal immunoglobulins (M-proteins) that drive complications but are inaccessible to CAR T-cell or antibody targeting. Peptides from IgA and IgG constant regions were eluted from HLA-A*02:01, and reactive TCRs were isolated from healthy donors using allo-HLA-A*02:01 presentation to circumvent self-tolerance. T cells engineered with two TCRs specific for IgA or IgG passed a stringent multi-tier safety screen and selectively eliminated MM cells from 20 HLA-A*02:01+ patients secreting the relevant IgH in vitro. In vivo, IgA-TCR T cells eradicated IgA+HLA-A*02:01+ MM cells in xenograft models and reduced circulating IgA in humanized PBMC mice. These findings establish immunoglobulin constant domains as viable TCR targets in MM, potentially making ~40% of patients of European descent eligible for TCR T cell therapy, and extension to additional HLA alleles could further broaden eligibility. The approach may also be applicable to lymphoma and antibody-mediated autoimmune diseases.

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Identification of HLA-A*11:01 and A*02:01-restricted EBV Pep-tides using HLA Peptidomics

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Mtb HLA-E tetramer sorted CD8+ T-cells have a diverse TCR repertoire

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