Effect of a Single Amino Acid Change in MHC Class I Molecules on the Rate of Progression to AIDS

摘要: Background From studies of genetic polymorphisms and the rate progression from human immunodeficiency virus type 1 (HIV-1) infection to acquired syndrome (AIDS), it appears that strongest susceptibility is conferred by major-histocompatibility-complex (MHC) class I HLA-B*35,Cw*04 allele. However, cytotoxic T-lymphocyte responses have been observed against HIV-1 epitopes presented HLA-B*3501, most common HLA-B*35 subtype. We examined subtypes in five cohorts analyzed relation structural differences between risk AIDS. Methods Genotyping HLA loci was performed for 850 patients who seroconverted had known dates infection. Survival analyses with respect AIDS were identify effects closely related different peptide-binding specificities. Results divided into two groups according specificity: HLA-B*35-PY group, which consists primarily HLA-B*3501 binds proline position 2 tyrosine 9; more broadly reactive HLA-B*35-Px also but can bind several amino acids (not including tyrosine) 9. The influence accelerating completely attributable alleles, some differ alleles only one acid residue. Conclusions This analysis shows that, infection, a single change molecules has substantial effect on consequences terms disease highlight importance epitope specificities immune defense HIV-1.