CD8+ T cell-mediated HLA-A*0201-restricted cytotoxicity to transaldolase peptide 168-176 in patients with multiple sclerosis.

Abstract

Transaldolase (TAL) is expressed at selectively high levels in oligodendrocytes and targeted by autoreactive T cells of patients with multiple sclerosis (MS). Among 14 TAL peptides with predicted HLA-A2 binding, TAL 168-176 (LLFSFAQAV, TALpep) exhibited high affinity for HLA-A2. Prevalence of HLA-A2-restricted CD8+ T cells specific for TALpep was increased in PBMC of HLA-A2+ MS patients, as compared with HLA-A2- MS patients, HLA-A2+ other neurological disease patients, and HLA-A2+ healthy donors. HLA-A*0201/TALpep tetramers detected increased frequency of TAL-specific CD8+ T cells, and precursor frequency of TAL-specific IFN-gamma-producing T cells was increased in each of seven HLA-A2+ MS patients tested. Stimulation by TALpep or rTAL of PBMC from HLA-A2+ MS patients elicited killing of TALpep-pulsed HLA-A2-transfected HmyA2.1 lymphoma cells, but not HLA-A3-transfected control HmyA3.1 targets. Without peptide pulsing of targets, HLA-A2-transfected, but not control MO3.13 oligodendroglial cells, expressing high levels of endogenous TAL, were also killed by CD8+ CTL of MS patients, indicating recognition of endogenously processed TAL. TCR Vbeta repertoire analysis revealed use of the TCR Vbeta14 gene by T cell lines (TCL) of MS patients generated via stimulation by TAL- or TALpep-pulsed APCs. All TAL-specific TCL-binding HLA-A*0201/TALpep tetramers expressed TCR Vbeta14 on the cell surface. Moreover, Ab to TCR Vbeta14 abrogated cytotoxicity by HLA-A2-restricted TAL-specific TCL. Therefore, TAL-specific CTL may serve as a novel target for therapeutic intervention in patients with MS.

• Authors: Brian Niland, Katalin Banki, William E Biddison, Andras Perl
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 175 Issue 12 Pg. 8365-78 (Dec 15 2005) ISSN: 0022-1767 [Print] United States
• PMID: 16339578 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• HLA-A Antigens
• HLA-A*02:01 antigen
• HLA-A2 Antigen
• Peptide Fragments
• Transaldolase

Topics

• Adult
• Aged
• Aged, 80 and over
• Amino Acid Sequence
• CD8-Positive T-Lymphocytes (immunology)
• Case-Control Studies
• Cytotoxicity, Immunologic
• Female
• HLA-A Antigens (immunology)
• HLA-A2 Antigen
• Humans
• Male
• Middle Aged
• Multiple Sclerosis (immunology, pathology)
• Oligodendroglia (enzymology)
• Peptide Fragments (immunology)
• T-Cell Antigen Receptor Specificity
• Transaldolase (immunology)