MAJOR HISTOCOMPATIBILITY COMPLEX RESTRICTION IN TUBERCULOSIS SUSCEPTIBILITY

More than one mechanism may contribute to disease susceptibility in tu berculosis, viz,, major histocompatability complex (MHC) restriction p henomenon, spectrum of immune reactivity/cytokine profile and epidemio logy 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 responde r status, (ii) spectrum of immune reactivity to mycobacteria is 'innat e', 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 respon der 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 pept ides and (v)majority of the T-cell clones generated in vitro, to pepti de 16.3 (amino acids 21-40) of 16 kDa 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, Nonetheles s the outcome and specificity of the immune reactivity and the resulta nt disease pathogenesis may depend on the promiscuity of peptide recog nition and cytokine profiles.