ARGININE AT POSITIONS 13 OR 70-71 IN POCKET-4 OF HLA-DRB1 ALLELES IS ASSOCIATED WITH SUSCEPTIBILITY TO TUBERCULOID LEPROSY

Evaluation of human histocompatibility leukocyte antigen (HLA) class I I genes in 54 cases of tuberculoid leprosy (TL) and 44 controls has sh own a positive association with HLA-DRB1 alleles that contain Arg(13) or Arg(70)-Arg(71). Among TL patients, 87% carry specific alleles of D RB1 Arg(13) or Arg(70)-Arg(71) as compared to 43% among controls (p = 5 X 10(-6)) conferring a relative risk of 8.8. Thus, susceptibility to TL involves three critical amino acid positions of the beta chain, th e side chains of which, when modeled on the DR1 crystal structure, lin e a pocket (pocket 4) accommodating the side chain of a bound peptide. This study suggests that disease susceptibility may be determined by the independent contribution of polymorphic residues participating in the formation of a functional arrangement (i.e., pocket) within the bi nding cleft of an HLA molecule.