A Subset of Human Autoreactive CD1c-Restricted T Cells Preferentially Expresses TRBV4-1+ TCRs

Tingxi Guo, Ming Yin Koo, Yuki Kagoya, Mark Anczurowski, Chung Hsi Wang, Kayoko Saso, Marcus O. Butler, Naoto Hirano

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)


In humans, a substantial portion of T cells recognize lipids presented by the monomorphic CD1 proteins. Recent studies have revealed the molecular basis of mycobacterial lipid recognition by CD1c-restricted T cells. Subsets of CD1c-restricted T cells recognize self-lipids in addition to foreign lipids, which may have implications in human diseases involving autoimmunity and malignancy. However, the molecular identity of these self-reactive T cells remains largely elusive. In this study, using a novel CD1c+ artificial APC (aAPC)-based system, we isolated human CD1c-restricted autoreactive T cells and characterized them at the molecular level. By using the human cell line K562, which is deficient in MHC class I/II and CD1 expression, we generated an aAPC expressing CD1c as the sole Ag-presenting molecule. When stimulated with this CD1c+ aAPC presenting endogenous lipids, a subpopulation of primary CD4+ T cells from multiple donors was consistently activated, as measured by CD154 upregulation and cytokine production in a CD1c-specific manner. These activated CD4+ T cells preferentially expressed TRBV4-1+ TCRs. Clonotypic analyses of the reconstituted TRBV4-1+ TCR genes confirmed CD1c-restricted autoreactivity of this repertoire, and the strength of CD1c reactivity was influenced by the diversity of CDR3b sequences. Finally, alanine scanning of CDR1 and CDR2 sequences of TRBV4-1 revealed two unique residues, Arg30 and Tyr51, as critical in conferring CD1c-restricted autoreactivity, thus elucidating the molecular basis of the observed V gene bias. These data provide new insights into the molecular identity of human autoreactive CD1c-restricted T cells.

Original languageEnglish
Pages (from-to)500-511
Number of pages12
JournalJournal of Immunology
Issue number2
Publication statusPublished - 2018 Jan 15
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


Dive into the research topics of 'A Subset of Human Autoreactive CD1c-Restricted T Cells Preferentially Expresses TRBV4-1+ TCRs'. Together they form a unique fingerprint.

Cite this