HLA-DRB1 leprogenic motifs in nigerian population groups.

Amino acid residues involved in the peptide binding groove of HLA-DRB1 alleles were examined in three Nigerian ethnic groups with leprosy (n = 287) and 170 controls to determine the role of DRB1 alleles in disease outcome with Mycobacterium leprae. Nine positively charged motifs and two others with neutral charge to the binding groove were detected. These motifs occurred more frequently in leprosy (leprogenic) than was expected by chance (P < 0.0001). In contrast, five motifs with net negative or 'modified' neutral charges to the pocket were negatively associated with leprosy. We conclude that clinical outcome of infection with M. leprae is largely determined by a shared epitope in DRB1 alleles marked by several motifs. These motifs occur in otherwise normal DRB1 alleles, characterized by net positive or neutral charges in the binding groove. We hypothesize that these polarities cause poor binding of DRB1 to M. leprae. On presentation, the signal via the T cell receptor results in muted cell-mediated immunity. The resulting response translates to various forms of leprosy depending on degree of charge consonance between M. leprae and host DRB1 allele. Other factors within or without the HLA complex, such as the T cell receptor repertoire, may also influence the resulting disease.

HLA class I phenotype and gene frequencies in parts of southern Nigeria.

HLA-A, B and C antigens were determined in 101 healthy subjects from two major and several minor ethnic groups in some parts of Southern Nigeria. Compared to earlier data based on a panel of expatriate Nigerians, significant differences were observed in antigen phenotype and gene frequencies particularly at the HLA-A locus. At least three antigenic specificities not previously observed in the expatriate Nigerians were detected in the present study. These included HLA-B8. B14 and CW1. These antigens however occurred at low frequencies. The antigens A23 and B7 were in positive linkage disequilibrium along with others which involved CW4 with B53 or B35. It is concluded from our findings that HLA polymorphisms in Nigerians may not be completely reflected in major population group studies alone. It is possible that more specificities may be detected by continued testing of the minor ethnic groups. The importance of this could be immense in disease association studies involving HLA genes as well as in anthropology.