Cytokine profile, HLA restriction and TCR sequence analysis of human CD4+ T clones specific for an immunodominant epitope of Mycobacterium tuberculosis 16-kDa protein

N. Caccamo, A. Barera, C. Di Sano, S. Meraviglia, J. Ivanyi, F. Hudecz, Sz. Bősze, Francesco Dieli, A. Salerno

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

The identification of immunodominant and universal mycobacterial peptides could be applied to vaccine design and have an employment as diagnostic reagents. In this paper we have investigated the fine specificity, clonal composition and HLA class II restriction of CD4+ T cell clones specific for an immunodominant epitope spanning amino acids 91-110 of the 16-kDa protein of Mycobacterium tuberculosis. Twenty-one of the tested 28 clones had a Th1 profile, while seven clones had a Th0 profile. None of the clones had a Th2 profile. While the TCR AV gene usage of the clones was heterogeneous, a dominant TCR BV2 gene family was used by 18 of the 28 clones. The CDR3 regions of BV2+ T cell clones showed variation in lengths, but a putative common motif R-L/V-G/S-Y/W-E/D was detected in 13 of the 18 clones. Moreover, the last two to three residues of the putative CDR3 loops, encoded by conserved BJ sequences, could also play a role in peptide recognition. Antibody blockade and fine restriction analysis using HLA-DR homozygous antigen-presenting cells established that 16 of 18 BV2+ peptide-specific clones were DR restricted and two clones were DR-DQ and DR-DP restricted. Additionally, five of the 18 TCRBV2+ clones recognized peptide 91-110 in association with both parental and diverse HLA-DR molecules, indicating their promiscuous recognition pattern. The ability of peptide 91-110 to bind a wide range of HLA-DR molecules, and to stimulate a Th1-type interferon (IFN)-γ response more readily, encourage the use of this peptide as a subunit vaccine component.

Original languageEnglish
Pages (from-to)260-266
Number of pages7
JournalClinical and Experimental Immunology
Volume133
Issue number2
DOIs
Publication statusPublished - Aug 1 2003

Fingerprint

Immunodominant Epitopes
Mycobacterium tuberculosis
Sequence Analysis
Clone Cells
Cytokines
Proteins
Peptides
HLA-DR Antigens
T-Lymphocytes
Subunit Vaccines
Conserved Sequence
Antigen-Presenting Cells
Interferons
Genes
Vaccines

Keywords

  • 16-kDa M. tuberculosis antigen
  • CD4T cells
  • HLA restriction
  • IFN-γ
  • T cell receptor

ASJC Scopus subject areas

  • Immunology

Cite this

Cytokine profile, HLA restriction and TCR sequence analysis of human CD4+ T clones specific for an immunodominant epitope of Mycobacterium tuberculosis 16-kDa protein. / Caccamo, N.; Barera, A.; Di Sano, C.; Meraviglia, S.; Ivanyi, J.; Hudecz, F.; Bősze, Sz.; Dieli, Francesco; Salerno, A.

In: Clinical and Experimental Immunology, Vol. 133, No. 2, 01.08.2003, p. 260-266.

Research output: Contribution to journalArticle

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