HLA-DRB1 leprogenic motifs in Nigerian population groups

Amino acid residues involved in the peptide binding groove of HLA-DRB1 alle les were examined in three Nigerian ethnic groups with leprosy (n = 287) an d 170 controls to determine the role of DRB1 alleles in disease outcome wit h Mycobacterium leprae. Nine positively charged motifs and two others with neutral charge to the binding groove were detected. These motifs occurred m ore frequently in leprosy (leprogenic) than was expected by chance (P < 0.0 001). In contrast, five motifs with net negative or 'modified' neutral char ges to the pocket were negatively associated with leprosy. We conclude that clinical outcome of infection with M. leprae is largely determined by a sh ared epitope in DRB1 alleles marked by several motifs. These motifs occur i n otherwise normal DRB1 alleles, characterized by net positive or neutral c harges in the binding groove. We hypothesize that these polarities cause po or binding of DRB1 to M. leprae. On presentation, the signal via the T cell receptor results in muted cell-mediated immunity. The resulting response t ranslates to various forms of leprosy depending on degree of charge consona nce between M. leprae and host DRB1 allele. Other factors within or without the HLA complex, such as the T cell receptor repertoire, may also influenc e the resulting disease.