The strongest susceptibility to progression from HIV-1 infection to AIDS is conferred by the major-histocompatibility-complex (MHC) class I type HLA-B*35,Cw*04 allele. In the May 31 New England Journal of Medicine, Xiaojiang Gao and colleagues from Johns Hopkins School of Medicine, Baltimore shows that a single amino-acid change in HLA molecules has a substantial effect on the rate of progression to AIDS.
Gao et al. genotyped HLA class I loci for 850 patients who seroconverted and had known dates of HIV-1 infection. HLA-B*35 subtypes were divided into two groups according to peptide-binding specificity: the HLA-B*35-PY group, which consists primarily of HLA-B*3501 and binds epitopes with proline in position 2 and tyrosine in position 9; and the more broadly reactive HLA-B*35-Px group, which also binds epitopes with proline in position 2 but can bind several different amino acids (excluding tyrosine) in position 9. Survival analyses showed a rapid progression to AIDS in patients with HLA-B*35-Px alleles and a slower progression in patients with HLA-B*35-PY alleles, some of which differ from HLA-B*35-Px by only one amino acid residue (NEJM 2001, 344:1668-1675).
The effect is probably attributable to an inappropriate cytotoxic-T-lymphocyte response in patients with HLA-B*35-Px, whereas a comparatively protective response occurs in patients with HLA-B*35-PY that corresponds with the slower progression to disease in these patients.
Gao X, Nelson GW, Karacki P, Martin MP, Phair J, Kaslow R, Goedert JJ, Buchbinder S, Hoots K, Vlahov D, et al.: Effect of a single amino acid change in MHC class I molecules on the rate of progression to AIDS. NEJM 2001, 344:1668-1675.
Johns Hopkins School of Medicine