Selection of hprt mutant T cells as surrogates for dividing cells reveals a restricted T cell receptor BV repertoire in insulin-dependent diabetes mellitus

Clin Immunol. 1999 Mar;90(3):340-51. doi: 10.1006/clim.1998.4664.

Abstract

T cells with somatically acquired mutations in the hypoxanthine-guanine phosphoribosyltransferase (hprt) gene were isolated from patients with insulin-dependent diabetes mellitus (IDDM) as representatives of populations potentially enriched for in vivo activated T cells. TCRB gene V region usage among mutant isolates from individual IDDM patients, but not from normal controls, showed a pronounced preference for BV14 and, to a lesser extent, BV6. Wild-type (nonmutant) isolates did not show such preferences. Extensive in vivo clonal expansions of the BV14 expressing mutant T cells from IDDM patients were revealed by sequence identity of TCRB chain junctional regions. These data support restricted TCRB gene usage in T cell populations enriched for in vivo activated clones in patients with IDDM.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Cloning, Molecular
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology*
  • Female
  • Gene Rearrangement, beta-Chain T-Cell Antigen Receptor*
  • Humans
  • Hypoxanthine Phosphoribosyltransferase / genetics*
  • Male
  • Mutation
  • Receptors, Antigen, T-Cell, alpha-beta / genetics*
  • T-Lymphocyte Subsets / immunology*

Substances

  • Receptors, Antigen, T-Cell, alpha-beta
  • Hypoxanthine Phosphoribosyltransferase