Lysis of interferon-γ activated Schwann cell by cross-reactive CD8+ ∝/β T cells with specificity for the mycobacterial 65 kd heat shock protein

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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.bovls/M.tuberculosis (>95% protein sequence homology) and surprisingly similar in man (65% protein sequence homology). Recently, we had provided evidence In a murlne model that CD8+ T cells recognize and lyse Schwann cells presenting M.leprae antigen in the context of major hlstocompatibility (MHC) class I gene products. Because murlne Schwann cells are class I negative, antigen presentation requires prior stimulation with interferon-γ (IFN-γ). CD8+ T cells were activatedagainst tryptic fragments of mycobacterial hsp 65. These T cells recognized epltopes 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-γ 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-γ and primed with ova peptides. Evidence Is presented that class I (H-2D) restricted, CD8+ α/β T lymphocytes with specificity for the mycobacterial hsp 65 recognize IFN-γ-stlmulated Schwann cells probably because they are specific for a(n) epltope(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 tuberculold leprosy which is characterized by low to absent M.leprae in Schwann cells.