Ex Vivo Analysis of Human T Lymphotropic Virus Type 1–Specific CD4⁺Cells by Use of a Major Histocompatibility Complex Class II Tetramer Composed of a Neurological Disease–Susceptibility Allele and Its Immunodominant Peptide

Abstract

HLA-DRB1*0101 is associated with susceptibility to human T lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Here, we used a synthetic tetramer of DRB1*0101 and its epitope peptide to analyze HTLV-1-specific CD4(+) T cells ex vivo. The frequency of tetramer(+)CD4(+) T cells was significantly greater in patients with HAM/TSP than in healthy HTLV-1 carriers (HCs) at a given proviral load and correlated with HTLV-1 tax messenger RNA expression in HCs but not in patients with HAM/TSP. These cells displayed an early to intermediate effector memory phenotype and were preferentially infected by HTLV-1. T cell receptor gene analyses of 2 unrelated DRB1*0101-positive patients with HAM/TSP showed similar Vbeta repertoires and amino acid motifs in complementarity-determining region 3. Our data suggest that efficient clonal expansion of virus-specific CD4(+) T cells in patients with HAM/TSP does not simply reflect higher viral burden but rather reflects a rapid turnover caused by preferential infection and/or in vivo stimulation by major histocompatibility complex-peptide complexes.

Cytomegalovirus (CMV) Epitope–Specific CD4+ T Cells Are Inflated in HIV+ CMV+ Subjects

“…Notably, some of the repertoires of these single epitope-specific T cells are diverse with over six unique, dominant TCR gene families (55, 73, 80, 83). Therefore, to our knowledge, our work represents the first combination of ex vivo , class II tetramer-derived and deep sequencing-based identification of a nearly monoclonal TCR repertoire of inflated HLA-restricted epitope-specific CD4 + T cells at the resolution of the CDR3.…”

MHC Class II Tetramers

“…Monitoring immunity to infectious pathogens. Class II tetramers have been used for analysis of a variety of human CD4 T cell responses to pathogens, including influenza A, Borrelia, EBV, CMV, Mycobacterium tuberculosis, human T-lymphotropic virus 1, hepatitis C, anthrax, severe acute respiratory syndrome virus, human papillomavirus, and HIV (3,7,(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). Ag-specific T cells are detected in peripheral blood, with a very broad range of frequency, depending on prior Ag exposure, vaccination history, and timing of immunization.…”

Genes Related to Antiviral Activity, Cell Migration, and Lysis Are Differentially Expressed in CD4+T Cells in Human T Cell Leukemia Virus Type 1-Associated Myelopathy/Tropical Spastic Paraparesis Patients

“…24 Thus, the potential contribution of CD4 T cells to the pathogenesis of this inflammatory disease as well as their expansion in HAM/TSP is more efficient due to the chronic antigenic stimulation that occurs in these individuals. 25,26 The aim of this work was to identify genes differentially expressed among healthy control (CT), asymptomatic HTLV-1 carrier (HAC), and HAM/TSP patients in CD4 + T cells isolated from these individuals. We showed that the global gene expression profile of circulating CD4 + T cells from HTLV-1 individuals harboring distinct clinical status was altered regardless of TAX expression levels.…”