02406nas a2200469   4500000000100000008004100001260001300042653001500055653001000070653000900080653001200089653002200101653001800123653001300141653001100154653001900165653002000184653002000204653003100224653001100255653001200266653000900278653001600287653001200303100001200315700001100327700001500338700001100353700001200364700001200376700001300388700001100401700001200412700001400424700001500438245006200453856007800515300001000593490000800603520131100611022001401922       1999                            d  c1999 Oct10aAdolescent10aAdult10aAged10aAlleles10aAmino Acid Motifs10aBinding Sites10aEpitopes10aFemale10aGene Frequency10aHLA-DR Antigens10aHLA-DRB1 Chains10aHistocompatibility Testing10aHumans10aleprosy10aMale10aMiddle Aged10aNigeria1 aUko G P1 aLu L Y1 aAsuquo M A1 aFici D1 aMahan S1 aAwdeh Z1 aUdim E R1 aDing W1 aUmana U1 aAdewole T1 aFraser P A00aHLA-DRB1 leprogenic motifs in nigerian population groups.  uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1905405/pdf/cei0118-0056.pdf  a56-620 v1183 a<p>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.</p>  a0009-9104