CROSS-RECOGNITION BY T-CELLS OF AN EPITOPE SHARED BY 2 UNRELATED MYCOBACTERIAL ANTIGENS

The molecular mimicry represented by cross-recognition of determinants shared by unrelated antigens by antibodies or T cells is of broad imm unological interest. In this study, we analyzed the cross-recognition by CD4(+) T cells of a peptide epitope shared by two mycobacterial pro teins of diverse sequence, represented by the 19-kDa antigen of Mycoba cterium tuberculosis and the 28-kDa antigen of Mycobacterium leprae. T his epitope was immunodominant with respect to the 19-kDa antigen, but cryptic in relation to the 28-kDa antigen. The cross-reactive epitope cores were identified by Pepscan window analysis and found to be eigh t residues long in both antigens (residues 69-76 and 127-134). Alignme nt of these octameric sequences revealed two identical and five conser vatively related amino acids. Within the epitope core, two residues (( 73)Asn and (76)Ile) were identified as critical for recognition on the basis of inhibition of the cross-reactive T cell proliferative respon se using singly substituted analog peptides. These results suggest tha t T cell cross-reactive epitopes can exist in proteins with apparently not more than random levels of sequence homology. Their potential for unsuspected cross-sensitization may play a role in the maintenance of T cell memory, in the pathogenesis of autoimmune diseases and possibl y in a wide range of host immune responses to infectious pathogens.