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T cell receptors recognizing Medicago sativa-derived peptides (TCR-alfalfa)

Target
TCR-alfalfa
Molecular classification
Receptor, T cell receptor
01

Overview

T cell receptors (TCRs) recognizing Medicago sativa-derived peptides are a specialized class of immune receptors that specifically bind to antigenic fragments from the alfalfa plant (Medicago sativa) presented on major histocompatibility complex (MHC) molecules. In the field of adoptive T-cell therapy (TCR-T), these receptors are frequently employed as negative controls in high-throughput specificity assays, such as T-Scan and PresentER, to validate the absence of off-target reactivity against human self-peptides. Because alfalfa-derived peptides, such as those from the Rubisco protein (e.g., the GLLGVAASV epitope), are absent from the human proteome, a TCR specific for these antigens should exhibit no reactivity toward human tissues, making it an ideal benchmark for identifying off-target cross-reactivity. Biologically, these TCRs are involved in the development of oral tolerance to dietary plant proteins and the mediation of allergic hypersensitivity reactions in sensitized individuals. Furthermore, research has linked the ingestion of alfalfa-derived non-canonical amino acids, such as L-canavanine, to the generation of neoepitopes that can be recognized by TCRs, potentially triggering or exacerbating autoimmune responses similar to Systemic Lupus Erythematosus (SLE). While not currently a primary therapeutic target for drug development, these TCRs are critical tools for ensuring the safety and precision of engineered T-cell immunotherapies.

Other names
Alfalfa-specific T-cell receptorMedicago-specific T-cell receptorTCR recognizing alfalfa peptidesTCR-alfalfaTCR recognizing Rubisco peptideMedicago sativa-specific TCR
02

Mechanism of action

Not applicable as this is primarily a research control or a mediator of hypersensitivity rather than a drug target.

03

Biological functions

Immune responseAntigen recognitionOral toleranceT-cell activation
04

Disease associations

AllergySystemic Lupus Erythematosus (SLE)InflammationAutoimmunity
05

Safety considerations

Cross-reactivity with human self-peptides (monitored via this control)Induction of autoimmune-like symptoms (e.g., lupus-like syndrome) upon ingestion of alfalfa seeds
06

Biomarkers

TCR repertoire analysisHLA-A*02:01 restrictionRubisco-specific T-cell frequency

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