Role of the MHC restriction during maturation of antigen-specific human T cells in the thymus

Eur J Immunol. 2016 Mar;46(3):560-9. doi: 10.1002/eji.201545951. Epub 2015 Dec 22.

Abstract

In the thymus, a T-cell repertoire able to confer protection against infectious and noninfectious agents in a peptide-dependent, self-MHC-restricted manner is selected. Direct detection of Ag-specific thymocytes, and analysis of the impact of the expression of the MHC-restricting allele on their frequency or function has never been studied in humans because of the extremely low precursor frequency. Here, we used a tetramer-based enrichment protocol to analyze the ex vivo frequency and activation-phenotype of human thymocytes specific for self, viral and tumor-antigens presented by HLA-A*0201 (A2) in individuals expressing or not this allele. Ag-specific thymocytes were quantified within both CD4CD8 double or single-positive compartments in every donor. Our data indicate that the maturation efficiency of Ag-specific thymocytes is poorly affected by HLA-A2 expression, in terms of frequencies. Nevertheless, A2-restricted T-cell lines from A2(+) donors reacted to A2(+) cell lines in a highly peptide-specific fashion, whereas their alloreactive counterparts showed off-target activity. This first ex vivo analysis of human antigen-specific thymocytes at different stages of human T-cell development should open new perspectives in the understanding of the human thymic selection process.

Keywords: Antigen · Human T cells · MHC · Tetramers · Thymocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation
  • Antigens, Neoplasm / immunology*
  • Antigens, Viral / immunology*
  • Autoantigens / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Line
  • Epitopes*
  • HLA-A2 Antigen / genetics
  • HLA-A2 Antigen / immunology*
  • Humans
  • Peptides / immunology
  • T-Lymphocytes / immunology*
  • Thymocytes / immunology
  • Thymocytes / physiology*
  • Thymus Gland / cytology
  • Thymus Gland / immunology

Substances

  • Antigens, Neoplasm
  • Antigens, Viral
  • Autoantigens
  • Epitopes
  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • Peptides