T细胞受体序列会影响T细胞记忆形成的可能性。

The T cell receptor sequence influences the likelihood of T cell memory formation.

作者信息

Lagattuta Kaitlyn A, Kohlgruber Ayano C, Abdelfattah Nouran S, Nathan Aparna, Rumker Laurie, Birnbaum Michael E, Elledge Stephen J, Raychaudhuri Soumya

机构信息

Center for Data Sciences, Brigham and Women's Hospital, Boston, MA, USA; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Department of Genetics, Harvard Medical School, Boston, MA, USA; Division of Immunology, Boston Children's Hospital, Boston, MA, USA.

出版信息

Cell Rep. 2025 Jan 28;44(1):115098. doi: 10.1016/j.celrep.2024.115098. Epub 2024 Dec 27.

DOI:10.1016/j.celrep.2024.115098

PMID:39731734

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11785489/

Abstract

The amino acid sequence of the T cell receptor (TCR) varies between T cells of an individual's immune system. Particular TCR residues nearly guarantee mucosal-associated invariant T (MAIT) and natural killer T (NKT) cell transcriptional fates. To define how the TCR sequence affects T cell fates, we analyze the paired αβTCR sequence and transcriptome of 961,531 single cells. We find that hydrophobic complementarity-determining region (CDR)3 residues promote regulatory T cell fates in both the CD8 and CD4 lineages. Most strikingly, we find a set of TCR sequence features that promote the T cell transition from naive to memory. We quantify the extent of these features through our TCR scoring function "TCR-mem." Using TCR transduction experiments, we demonstrate that increased TCR-mem promotes T cell activation, even among T cells that recognize the same antigen. Our results reveal a common set of TCR sequence features that enable T cell activation and immunological memory.

摘要

个体免疫系统中T细胞的T细胞受体（TCR）氨基酸序列各不相同。特定的TCR残基几乎决定了黏膜相关恒定T（MAIT）细胞和自然杀伤T（NKT）细胞的转录命运。为了确定TCR序列如何影响T细胞命运，我们分析了961,531个单细胞的配对αβTCR序列和转录组。我们发现，疏水互补决定区（CDR）3残基在CD8和CD4谱系中均促进调节性T细胞命运。最引人注目的是，我们发现了一组促进T细胞从幼稚状态转变为记忆状态的TCR序列特征。我们通过TCR评分函数“TCR-mem”对这些特征的程度进行量化。通过TCR转导实验，我们证明即使在识别相同抗原的T细胞中，增加的TCR-mem也能促进T细胞活化。我们的结果揭示了一组共同的TCR序列特征，这些特征能够实现T细胞活化和免疫记忆。