@article{7345, keywords = {Animals, Antibodies, Monoclonal, Bacterial Proteins, Cross Reactions, Epitopes, Heat-Shock Proteins, Humans, Interferon-gamma, Leprosy, Tuberculoid, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Mycobacterium bovis, Mycobacterium tuberculosis, Recombinant Proteins, Schwann Cells, T-Lymphocytes, Cytotoxic}, author = {Steinhoff U and Schoel B and Kaufmann S H}, title = {Lysis of interferon-gamma activated Schwann cell by cross-reactive CD8+ alpha/beta T cells with specificity for the mycobacterial 65 kd heat shock protein.}, abstract = {

Heat shock protein (hsp) 65 is a major T cell antigen of Mycobacterium leprae. The hsp 65 of M. leprae is nearly identical in M. bovis/M. tuberculosis (greater than 95% protein sequence homology) and surprisingly similar in man (65% protein sequence homology). Recently, we had provided evidence in a murine model that CD8+ T cells recognize and lyse Schwann cells presenting M. leprae antigen in the context of major histocompatibility (MHC) class I gene products. Because murine Schwann cells are class I negative, antigen presentation requires prior stimulation with interferon-gamma (IFN-gamma). CD8+ T cells were activated against tryptic fragments of mycobacterial hsp 65. These T cells recognized epitopes of hsp 65 which had been generated through the cytoplasmic class I processing pathway. They were also capable of lysing Schwann cells which had been activated by IFN-gamma and not primed with nominal hsp 65 peptides. In contrast, T cells activated against tryptic ova peptides only lysed Schwann cells which had been both stimulated with IFN-gamma and primed with ova peptides. Evidence is presented that class I (H-2D) restricted, CD8+ alpha/beta T lymphocytes with specificity for the mycobacterial hsp 65 recognize IFN-gamma-stimulated Schwann cells probably because they are specific for a(n) epitope(s) shared by the bacterial hsp and a host cognate. Activation of autoreactive T cells with specificity to shared epitopes could contribute to nerve damage in tuberculoid leprosy which is characterized by low to absent M. leprae in Schwann cells.

}, year = {1990}, journal = {International immunology}, volume = {2}, pages = {279-84}, month = {1990}, issn = {0953-8178}, doi = {10.1093/intimm/2.3.279}, language = {eng}, }