02586nas a2200361   4500000000100000008004100001260000900042653001200051653002700063653002300090653002000113653001300133653002400146653001100170653002100181653002500202653002600227653000900253653002300262653002400285653003100309653002500340653001800365653002900383100001600412700001300428700001700441245016000458300001100618490000600629520157500635022001402210       1990                            d  c199010aAnimals10aAntibodies, Monoclonal10aBacterial Proteins10aCross Reactions10aEpitopes10aHeat-Shock Proteins10aHumans10aInterferon-gamma10aLeprosy, Tuberculoid10aLymphocyte Activation10aMice10aMice, Inbred C57BL10aMycobacterium bovis10aMycobacterium tuberculosis10aRecombinant Proteins10aSchwann Cells10aT-Lymphocytes, Cytotoxic1 aSteinhoff U1 aSchoel B1 aKaufmann S H00aLysis of interferon-gamma activated Schwann cell by cross-reactive CD8+ alpha/beta T cells with specificity for the mycobacterial 65 kd heat shock protein.  a279-840 v23 a<p>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.</p>  a0953-8178