ABSTRACT
More than one mechanism may contribute to disease susceptibility in tuberculosis, viz., major histocompatability complex (MHC) restriction phenomenon, spectrum of immune reactivity/cytokine profile and epidemiology induced anergy. Experiments from our laboratories revealed that (i) human leucocyte antigen D-related allele 2 (HLA DR2) predispose for a more severe form of pulmonary tuberculosis encoding a high responder status, (ii) spectrum of immune reactivity to mycobacteria is 'innate', and it is demonstrable in healthy individuals from endemic area, (iii) there is no correlation between the purified protein derivative (PPD) response and peptide responses, (iv) once a person is high responder to P16 and P38 derived peptides (6/22), he/she (whether a patient or control) is a high responder for a wide range of mycobacterial peptides and (v)majority of the T-cell clones generated in vitro, to peptide 16·3 (amino acids 21-40) of 16 kA a mycobacterial antigen, in an HLA DR2 positive healthy individual is HLA DR restricted, permissive and of Th1 phenotype. The results suggested that MHC class II restriction play a role in peptide recognition and the immune response. Nonetheless the outcome and specificity of the immune reactivity and the resultant disease pathogenesis may depend on the promiscuity of peptide recognition and cytokine profiles.
ABSTRACT
Cytotoxic T lymphocytes (CTL) derived from the spleen of SW-1 mice immunized in vivo with syngeneic mouse leukemia clonal cells LAC-1 were cultured in TCGF containing media and tested for cytotoxicity against LAC-1 cells in a routine ~(51)Cr-release assay. The experimental results showed that the CTL cell line was proved to be Thy 1 and Lyt 2, and therefore they were considered to be of T cell lineage. When CTL were expanded in the presence of TCGF, an augmented cytolytic activity in parallel with the increase of Thy 1 and Lyt 2 cells was shown. This cytotoxic T cell line had been maintained in a long-term culture for nearly 1 year and retained the initial reactivity. Specificity studies of the CTL showed that the cell line was highly specific for LAC-1 cells and its parent line L783 Leukemic cells and the cytolytic effect was H-2 restriction. The cytotoxicity of the CTL could be blocked by conventional or monoclonal antibodies against cell surface antigen (TSA) of LAC-1 cells. Antisera against H-2 antigens, shared by LAC-1 cells, also showed blocking activity.