Grouping HLA-B locus serologic specificities according to shared structural motifs suggests that different peptide-anchoring pockets may have contrasting influences on the course of HIV-1 infection.

Two different groups of HLA-B specificities were associated with two contrasting outcomes of HIV-1 infection. HLA-B45, -B49, and -B50 were each found at a moderately increased frequency among individuals responding to HIV-1 infection with a marked circulating and infiltrative CD8 T-cell lymphocytosis, a slow rate of CD4 T-cell decline, very low frequency of opportunistic infections, and low viral strain heterogeneity. In contrast, among HIV-infected individuals with more rapid progression to opportunistic infections, HLA-B35 was found to be increased in frequency and to act as a dominant marker for this adverse outcome. HLA-B45, -B49, and -B50 contain identical peptide-anchoring "B" and "C-terminal" pocket structures, which differ greatly from those present in HLA-B35, implying that different immunogenic peptides are likely to be bound by these two groups of alleles. Placing HLA-B45, -B49, and -B50 into one structurally defined group revealed a much stronger and statistically significant association with the CD8 lymphocytosis syndrome (OR = 5.3, p = 0.0005). The B pocket structure in these alleles contains an easily accessible lysine residue at position 45, suggesting that the P2 or P3 anchor residue of a bound peptide is negatively charged. Additionally, by observing the effect on the ORs of adding structures containing amino acid substitutions in the C-terminal pocket of HLA-B45, -B49, and -B50, this region was also shown to influence susceptibility to this host response.(ABSTRACT TRUNCATED AT 250 WORDS)