title: HLA-B may be more protective against HIV-1 than HLA-A because it resists negative regulatory factor (Nef) mediated down-regulation.
abstract: Human leukocyte antigen HLA-B alleles have better protective activity against HIV-1 than HLA-A alleles, possibly due to differences in HLA-restricted HIV-1-specific CD8+ cytotoxic T lymphocyte (CTL) function, but the mechanism is unknown. HIV-1 negative regulatory factor (Nef) mediates down-regulation of surface expression of class I HLA (HLA-I) and may therefore impair immune recognition by CTL. Because of sequence differences in the cytoplasmic domains, HLA-A and -B are down-regulated by Nef but HLA-C and -E are not affected. However, the latter are expressed at low levels and are not of major importance in the CTL responses to HIV-1. Here, we compared the role of the cytoplasmic domains of HLA-A and -B in Nef-mediated escape from CTL. We found HLA-B cytoplasmic domains were more resistant to Nef-mediated down-regulation than HLA-A cytoplasmic domains and demonstrated that these differences affect CTL recognition of virus-infected cells in vitro. We propose that the relative resistance to Nef-mediated down-regulation by the cytoplasmic domains of HLA-B compared with HLA-A contributes to the better control of HIV-1 infection associated with HLA-B-restricted CTLs.
authors: Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine,  University of Oxford, Oxford OX3 9DS,  United Kingdom.
authors: Ushani S
authors: US
authors: Rajapaksa
authors: Demin
authors: D
authors: Li
authors: Yan-Chun
authors: YC
authors: Peng
authors: Andrew J
authors: AJ
authors: McMichael
authors: Tao
authors: T
authors: Dong
authors: Xiao-Ning
authors: XN
authors: Xu
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D002460:Cell Line; D003593:Cytoplasm / Q000276:immunology; D015536:Down-Regulation / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D015234:HLA-A Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015235:HLA-B Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015793:HLA-B7 Antigen / Q000276:immunology; D015236:HLA-C Antigens / Q000737:chemistry / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000276:immunology; D016415:Sequence Alignment; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000821:virology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D000939:Epitopes; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015793:HLA-B7 Antigen; D015236:HLA-C Antigens; D011994:Recombinant Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus